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Biomedical subjects

U Wagner

Publications and source records attributed to U Wagner.

At least 37 records · Page 2Linked to original sources
PubMed2004

Survival chances and psychological aspects of quality of life in patients with localized early stage breast cancer.

BACKGROUND: The present analysis focuses on the long term psychological reactions to early stage breast cancer. Two hypotheses were formulated. The first hypothesis draws a direct link between tumour size/survival chances and Quality of life (QoL): The better the survival chances, the better QoL ('biological danger model'). The second hypothesis assumes that localized early breast cancer has excellent prognosis (> 90% five year survival rate), and that therefore QoL differences between various forms of early breast cancer should be minimal ('medico-pragmatic model'). PATIENTS AND METHODS: In a defined rural area with 252.000 inhabitants (small-area-analysis), a total of n = 389 patients with primary breast cancer were recruited. For the present analysis we selected a subgroup (n = 269) from the cohort by tumour size (pTis, pT1a,b, pT1c, and pT2). QoL scores for global quality of life, emotional functioning and future perspective were computed according to the EORTC manual and compared to age-matched norm data of the German population. RESULTS: A total of 690 QoL questionnaires were obtained from n = 269 patients with comparable completion rates within the four subgroups (pTis, pT1a,b, pT1c, and pT2). For all four groups and in all scores there were improvements over time. Generally, pTis always scored highest, pT2 always lowest, the other two groups in between. After one year pTis patients had higher mean scores in global quality of life than the norm. In contrast, pT1a,b were considerably lower than the norm and the difference between these two was 17.2 score points. It seems that the small difference (3.5%) in five year survival chances between pTis and T1 a,b tumours transforms into marked differences regarding quality of life, thus supporting a biological danger model of the survival/QoL relationship. CONCLUSIONS: Our results show that physicians have to realise although their early breast cancer patients have excellent survival chances, psychological distress is present. From a clinical perspective we would recommend that early stage breast cancer patients, and especially patients with occult, pT1a,b tumours be informed about their excellent prognosis. In addition, cognitive therapy might help patients stop worrying about their cancer.

Breast Neoplasms↗
PubMed2004

Laboratory measurements of 0.7 GG magnetic fields generated during high-intensity laser interactions with dense plasmas.

We report measurements of ultrahigh magnetic fields produced during intense ( approximately 10(20) Wcm(-2) micro m(2) ) laser interaction experiments with solids. We show that polarization measurements of high-order vuv laser harmonics generated during the interaction (up to the 15th order) suggest the existence of magnetic field strengths of 0.7+/-0.1 GG in the overdense plasma. Measurements using higher order harmonics indicate that denser regions of the plasma can be probed. This technique may be useful for measurements of multi- GG level magnetic fields which are predicted to occur at even higher intensities.

Journal Article↗
PubMed2004

Harmonic emission from the rear side of thin overdense foils irradiated with intense ultrashort laser pulses.

The harmonic emission from thin solid carbon and aluminum foils, irradiated by 150 fs long frequency-doubled Ti:sapphire laser pulses at lambda=395 nm and peak intensities of a few 10(18) W/cm(2), has been studied. In addition to the harmonics emitted from the front side in the specular direction, we observe harmonics up to the 10th order, including the fundamental from the rear side in the direction of the incident beam, while the foil is still strongly overdense. The experimental observations are well reproduced by particle-in-cell simulations. They reveal that strong coupling between the laser-irradiated side and the rear side occurs via the nonlocal electron current driven by the laser light.

Journal Article↗
PubMed2004

Docetaxel and carboplatin as first-line chemotherapy in patients with advanced gynecological tumors. A phase I/II trial of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO-OVAR) Ovarian Cancer Study Group.

OBJECTIVES: We performed a phase I-II study in patients with ovarian and other gynecological cancers to determine the dose-limiting toxicities, maximum tolerated dose (MTD) and efficacy of docetaxel/carboplatin. METHODS: Thirty patients were treated in three cohorts with carboplatin (AUC 5) and escalating docetaxel (60, 75 and 90 mg/m2), administered intravenously on day 1, repeated every 3 weeks. Premedication consisted of 16 mg dexamethasone per os on day -1, and +1 and 4 mg intravenously before docetaxel. RESULTS: A total of 6, 11 and 12 patients were eligible and treated on dose levels 1, 2 and 3, respectively. At docetaxel 90 mg/m2, febrile and prolonged neutropenia were dose-limiting, and 75 mg/m2 with carboplatin AUC 5 was considered the MTD. Prolonged neutropenia occurred in two, four and nine patients of dose levels 1-3, respectively, and febrile neutropenia in 2, 1, and 2 patients of dose level 1-3. Thrombocytopenia grade 4 was observed in one patient of dose level 1. Non-hematological toxicity including neuropathy was usually mild across all dose levels. Overall response rate was 73%. Median time to progression was 18.0 months, and median overall survival will exceed 24.4 months. CONCLUSIONS: Docetaxel/carboplatin can be safely administered to patients with gynecological cancer despite substantial myelotoxicity and appears to be active in the treatment of ovarian cancer. Low neurotoxicity offers an option for comparison with paclitaxel-containing regimens.

Adult↗
PubMed2004

[Differential diagnosis of Poland-syndrome versus unilateral accentuated thelarche].

AIM: The syndrome was first described by Poland in 1841. It classically consists of unilateral muscular and osseous anomalies of the thorax and upper limb with defects of the ipsilateral breast and nipple. We report the value of panoramic-sonography in the diagnosis of this rare condition in three patients. METHOD: The three girls, all born in 1990, were independently introduced to our unit of children and adolescent gynaecology because of unilateral "developmental defects" of the breasts at the beginning of puberty. To discriminate a Poland-Syndrome from unilateral accentuation of thelarche standardized clinical and sonographical examinations were performed. RESULTS: In 2 cases we found unilateral aplasia of the glandular tissue of the breast with different distinction of mamilla and pectoralis muscle. The 3 (rd) case showed a hypoplastic breast development with osseous defects of the chest wall, aplasia of the pectoralis muscle and brachydaktylia. CONCLUSION: The standardized panoramic sonography allowed an immediate and safe diagnosis without hazardous radiation exposure.

Adolescent↗
PubMed2004

[Vasoactive intestinal polypeptide in the respiratory tract: physiology and pathophysiology].

Peptidergic neuromediators have gained importance in the field of respiratory physiology and pathophysiology due to the characterisation of numerous pulmonary effects in the past years. With regard to the multitude of mediators, the neuropeptide vasoactive intestinale polypeptide (VIP) plays a special role as it exerts potent anti-inflammatory and immunomodulatory effects. Neurophysiologically the peptide has been attributed to the family of the inhibitory non-adrenergic non-cholinergic (i-NANC) neuromediators of the pulmonary innervation. VIP-containing nerve fibres are localized in the airway and vascular smooth muscle layers of trachea and bronchi in the human respiratory tract. Apart from strong vasodilatory effects, the peptide also shows a high bronchodilatory potency. In a large number of respiratory diseases VIP may play a pathophysiological role. In this respect, increased levels of VIP have been demonstrated for inflammatory diseases of the upper and lower airways and the peptide may also play a role in pulmonary hypertension. Due to its fast enzymatic cleavage, VIP-based therapies have not been used in routine therapy so far. Also, the use of synthetic VIP-agonists did not lead to an improved outcome in patients with bronchial asthma if compared to classical drugs. However, recent data from animal experiments indicate potent immunomodulatory effects which suggest a future use of this mediator and its agonists in the therapy of immune diseases.

Anti-Inflammatory Agents↗
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

Current approaches in ovarian cancer vaccines.

Much of the current approaches in the treatment of advanced ovarian cancer are directed towards prolongation of duration between primary treatment and remission. Immunotherapy is regarded as one attractive option for consolidation of initial therapeutic responses. In fact, immune reactivity against ovarian carcinoma can be induced by various immunotherapeutical approaches including antibodies, peptides or dendritic cell vaccines. This review provides an overview of recent clinical trials using various concepts of immunotherapy for the treatment of ovarian cancer. Possible reasons for limited clinical success as well as further progress to improve efficacy of current immune intervention strategies, e.g. by vaccines targeting a broader range of tumor-derived antigenic structures or activating diverse host immune functions, will be discussed.

Antibodies, Monoclonal↗
PubMed2003

Proton acceleration from high-intensity laser interactions with thin foil targets.

Measurements of energetic proton production resulting from the interaction of high-intensity laser pulses with foil targets are described. Through the use of layered foil targets and heating of the target material we are able to distinguish three distinct populations of protons. One high energy population is associated with a proton source near the front surface of the target and is observed to be emitted with a characteristic ring structure. A source of typically lower energy, lower divergence protons originates from the rear surface of the target. Finally, a qualitatively separate source of even lower energy protons and ions is observed with a large divergence. Acceleration mechanisms for these separate sources are discussed.

Journal Article↗
PubMed2003

Focal motility determines the geometry of dendritic spines.

The geometry of dendritic spines has a major impact on signal transmission at excitatory synapses. To study it in detail we raised transgenic mice expressing an intrinsic green fluorescent protein-based plasma membrane marker that directly visualizes the cell surface of living neurons throughout the brain. Confocal imaging of developing hippocampal slices showed that as dendrites mature they switch from producing labile filopodia and polymorphic spine precursors to dendritic spines with morphologies similar to those reported from studies of adult brain. In images of live dendrites these mature spines are fundamentally stable structures, but retain morphological plasticity in the form of actin-rich lamellipodia at the tips of spine heads. In live mature dendrites up to 50% of spines had cup-shaped heads with prominent terminal lamellipodia whose motility produced constant alterations in the detailed geometry of the synaptic contact zone. The partial enveloping of presynaptic terminals by these cup-shaped spines coupled with rapid actin-driven changes in their shape may operate to fine-tune receptor distribution and neurotransmitter cross-talk at excitatory synapses.

Animals↗
PubMed2003

Analysis of exotoxins produced by atypical isolates of Aeromonas salmonicida, by enzymatic and serological methods.

In this study, exotoxins produced by 62 Aeromonas salmonicida strains and the bacterium Haemophilus piscium were analysed. Enzymatic assays, zymograms and serological detection were used to monitor secretion by bacterial strains of the previously described exotoxins P1, GCAT and AsaP1 and also the extracellular P2 metallo-gelatinase and a serine caseinase, which is different from the P1 protease and has not yet been characterized. Based on the results, the strains were divided into five groups. One comprised the type strains for A. salmonicida ssp. masoucida, H. piscium and 36% of the atypical isolates, and another, a type strain for A. salmonicida ssp. smithia together with 14% of the atypical isolates. A second type strain of A. salmonicida ssp. smithia was grouped with 8% of the atypical isolates. The largest group contained the type strains for A. salmonicida ssp. achromogenes and 38% of the atypical isolates. The type strains for A. salmonicida ssp. salmonicida were in the last group with all the four typical strains and 4% of the atypical isolates. The combination of zymogram and serological detection used is recommended as the most reliable method for characterizing A. salmonicida strains according to their exotoxin secretion.

Aeromonas↗
PubMed2003

Fundamentals of pulmonary drug delivery.

Aerosol administration of peptide-based drugs plays an important role in the treatment of pulmonary and systemic diseases and the unique cellular properties of airway epithelium offers a great potential to deliver new compounds. As the relative contributions from the large airways to the alveolar space are important to the local and systemic availability, the sites and mechanism of uptake and transport of different target compounds have to be characterized. Among the different respiratory cells, the ciliated epithelial cells of the larger and smaller airways and the type I and type II pneumocytes are the key players in pulmonary drug transport. With their diverse cellular characteristics, each of these cell types displays a unique uptake possibility. Next to the knowledge of these cellular aspects, the nature of aerosolized drugs, characteristics of delivery systems and the depositional and pulmonary clearance mechanisms display major targets to optimize pulmonary drug delivery. Based on the growing knowledge on pulmonary cell biology and pathophysiology due to modern methods of molecular biology, the future characterization of pulmonary drug transport pathways can lead to new strategies in aerosol drug therapy.

Administration, Inhalation↗
PubMed2003

Prospective analysis of the impact of HLA-DR and -DQ on joint destruction in recent-onset rheumatoid arthritis.

OBJECTIVE: To evaluate the differential impact of HLA-DR and -DQ on the progression of erosive disease in the clinical course of early rheumatoid arthritis (RA). METHODS: HLA genotyping for HLA-DR and -DQ was carried out in a prospective study of 87 patients with early RA. The progression of erosive disease was assessed by radiological scores over a period of 2 yr in all patients and over 4 yr in 77 patients. The impact of HLA markers was evaluated by univariate comparisons and by multiple logistic regression analyses. RESULTS: Patients expressing the RA-associated shared epitope (SE) on a DRB1*01-positive or, most prominently, on a DRB1*04-positive allele had higher Larsen scores at all time-points analysed when compared with SE-negative patients. A similar impact on radiological progression was seen for the RA-predisposing DQ3, but not for DQ5 heterodimers. In the presence or absence of the DRB1 SE, no additional effects could be discerned for RA-associated DQ molecules. The presence of a DERAA-positive DRB1 allele was associated with a slower pace of joint destruction. While gene dosage effects were seen for SE compound homozygosity, no effect for DQ3 homozygosity could be discerned. CONCLUSION: Although a significant influence of HLA-DQ3 heterodimers on the progression of erosive joint destruction was seen, the analysis of the HLA-DQ locus did not add additional information over the study of HLA-DR including the determination of the SE and the DERAA motif in order to predict the development of severe progressive joint destruction.

Adult↗
PubMed2003

State-of-the-art first-line treatment of ovarian cancer.

Ovarian cancer is the fifth most frequent cause of death in women and, when related to the number of patients affected, the most common cause of death from gynecological malignancies. Recently, a number of new developments emerged. These refer to surgical as well as medical therapies and encompass the early stages FIGO I-IIA and the advanced stages FIGO IIB-IV. In particular, there were new findings on the significance of chemotherapy in the early stages as well as the significance of surgery in general, on the ideal timing of surgery in advanced stages, and new findings in the area of chemotherapy of advanced stages. All items are discussed in detail.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Mouse models of human cancer web-based resources.

The Mouse Models of Human Cancers Consortium (MMHCC) is a collaborative program designed to derive and characterize mouse models of human malignancies. To enhance information and resource exchange among the MMHCC investigators and other cancer research scientists, the NCI Center for Bioinformatics (NCICB, http://ncicb.nci.nih.gov/) has developed web-based resources that are freely available to the cancer research community. These resources include a website (http://emice.nci.nih.gov) and databases for cancer models (http://cancermodels.nci.nih.gov) and cancer images (http://cancerimages.nci.nih.gov).

Animals↗
PubMed2002

The role of neoadjuvant chemotherapy and interval laparotomy in advanced ovarian cancer.

Radical debulking surgery allows for optimal cytoreduction in less than 50% of patients with advanced ovarian cancer. In spite of highly efficient chemotherapeutic regimens, the prognosis of patients with residual tumor masses larger than 1 cm in diameter following staging laparotomy is very poor. This observation led to the initiation of numerous trials evaluating the feasibility and efficiency of the use of primary chemotherapy followed by interval laparotomy in women with advanced ovarian cancer. The available data is presented and discussed in this review.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Measuring huge magnetic fields.

Huge magnetic fields are predicted to exist in the high-density region of plasmas produced during intense laser-matter interaction, near the critical-density surface where most laser absorption occurs, but until now these fields have never been measured. By using pulses focused to extreme intensities to investigate laser-plasma interactions, we have been able to record the highest magnetic fields ever produced in a laboratory--over 340 megagauss--by polarimetry measurements of self-generated laser harmonics.

Journal Article↗