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Biomedical subjects

U Wagner

Publications and source records attributed to U Wagner.

At least 19 recordsLinked to original sources
PubMed2006

Bone mass and the risk of breast cancer: the influence of cumulative exposure to oestrogen and reproductive correlates. Results of the Marburg breast cancer and osteoporosis trial (MABOT).

BACKGROUND: Recent studies suggest an inverse relation between breast cancer and osteoporosis. Oestrogen is important in the pathophysiology of both breast and bone, and although cumulative exposure to oestrogen may explain the link between breast cancer and bone mass, this has never been proved. The Marburg breast cancer and osteoporosis trial (MABOT) aimed to elucidate the relation between breast cancer and bone mass ascertained by ultrasonometry measurement and to investigate whether endogenous and exogenous exposure to oestrogen and reproductive correlates has a role in this association. METHODS: We performed a case-control study including 2492 women (mean age+/-S.D., 54.4+/-10.3 years) in whom diseases and drug treatments known to affect bone metabolism, except for HT, had been excluded. All women underwent ultrasonometry measurement at the heel; 242 of the women had an incident breast cancer without a prior, specific pharmacological breast cancer treatment. The ultrasonometry variables - speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) - were calculated and compared in women with and without breast cancer. Because of significant intergroup differences in factors such as age, body mass index and exposure to oestrogen, a multiple linear regression analysis as well as a second analysis of ultrasonometry variables was undertaken using a randomly selected sample of 242 healthy women post-matched with the breast cancer group for possible confounding variables. Odds ratios were used to compare the relation between breast cancer risk and ultrasonometry heel measurements. RESULTS: Women with breast cancer were significantly older, weighed more, had a higher body mass index, were more likely to be parous and to have breast fed, were older at the menopause and had been exposed to oestrogen for longer than control women. In addition, the ultrasonometry variables speed of sound and the stiffness index T- and Z-score were significantly higher in women with breast cancer even after a matched pair analysis was performed (p<0.001). Additionally, results of a multiple linear regression showed that women with breast cancer had a significantly higher SOS (p<0.001), body weight (p<0.05) and duration of breast feeding (p<0.05) while osteoporotic fracture were reduced (p<0.001). When women with breast cancer and their matched controls were finally grouped according to SOS and T-score quartiles, the odds ratios (95% confidence intervals) for breast cancer risk in the second, third and fourth quartiles compared with the lowest quartile were 2.5 (1.4-4.3), 3.1 (1.8-5.3) and 4.7 (2.7-8.2) as well as 1.9 (1.1-3.2), 2.3 (1.3-3.9) and 2.9 (1.7-5.0), respectively. CONCLUSIONS: The ultrasonometry variables speed of sound, stiffness index, T- and Z-score are higher in women with an incident breast cancer than in healthy controls, even after post-matching for possible confounding variables. This association was confirmed in a multiple linear regression model. Women with SOS and T-score values in the higher quartiles have a greater risk of breast cancer than women in the lowest quartile. We found no association between the higher ultrasonometry variables and cancer specific characteristics or reproductive correlates such as age at menarche and menopause or cumulative oestrogen exposure. Although the biological mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than reproductive correlates, endogenous and exogenous exposure to oestrogen must play a part.

Adult↗
PubMed2006

Antibodies against cyclic citrullinated peptide are associated with the DRB1 shared epitope and predict joint erosion in rheumatoid arthritis.

OBJECTIVE: To evaluate antibodies against cyclic citrullinated peptide (anti-CCP antibodies) for their predictive value for severe joint destruction in rheumatoid arthritis (RA) and to examine their relationship to shared epitope (SE)-positive DRB1 alleles. METHODS: Concentrations of anti-CCP antibodies were determined in sera from 126 patients with recent onset RA who had been followed prospectively for 6 yr. Progression of joint destruction was evaluated according to Larsen by scoring radiographs from the hand and feet taken at baseline and after 1, 2, 4 and 6 yr of observation. In addition to clinical parameters, the presence of SE-positive DRB1 alleles and of rheumatoid factor IgM and IgA was determined. RESULTS: Anti-CCP antibodies were found more frequently and in higher concentrations in both DRB1*01-positive and in DRB1*04-positive SE-positive patients compared with SE-negative patients. Severe joint destruction as defined by a Larsen score in the upper third of the study population was predicted by positivity for anti-CCP antibodies, by the presence of SE-positive DRB1*04 alleles and by the presence of erosive disease at initial presentation. Multiple logistic regression analysis revealed that SE-positive DRB1*04 alleles and anti-CCP antibodies exerted a significant influence on the progression of joint destruction. CONCLUSION: The association of anti-CCP antibodies with DRB1*01 and with SE-positive DRB1*04 alleles implies a functional role for the SE sequence motif. The determination of SE-positive DRB1*04 alleles and of anti-CCP antibody positivity facilitates the prediction of disease course and prognosis at the time of initial presentation.

Adult↗
PubMed2006

[Rheumatoid arthritis and cardiovascular complications].

Rheumatoid arthritis is associated with increased morbidity and mortality due to cardiovascular events. Elevated concentrations of acute-phase proteins and cytokines and endothelial dysfunction, demonstrated also by lack of traditional risk factors, play an important role in these complications. Antirheumatic drug treatment can modify the frequency and severity of cardiovascular events.

Antirheumatic Agents↗
PubMed2006

[Diagnosis and treatment of malignant ovarian tumors 2005: recommendations of the Kommission Ovar of the AGO].

Recommendations for diagnosis and treatment of malignant ovarian tumors with regard to the most recent data were worked out in a consensus process and valued by level of evidence (LoE) and grade of recommendation (GoR) of the Canadian Task Force for Preventive Health Care by the members of the Kommission Ovar der Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) in June 2005. A short version of these guidelines is presented.

Aged↗
PubMed2006

Promoter polymorphisms regulating corticotrophin-releasing hormone transcription in vitro.

To investigate whether polymorphisms in the corticotrophin-releasing hormone (CRH) promoter are associated with altered CRH gene regulation, we studied the reactivity of three recently described promoter variants in vitro. The 3625 bp variants A1B1, A2B1 and A2B2 of the human CRH promoter were cloned in the 5' region to a luciferase reporter gene and transiently transfected into both mouse anterior pituitary cells AtT-20D16vF2 and pheochromocytoma cells PC12. Incubation with 8-Br-cAMP alone or in combination with cytokines significantly enhanced the promoter activity in both cell lines studied by up to 22-fold. However, dexamethasone antagonised cAMP effects on CRH expression in AtT-20 cells while showing no effect on PC12 cells, indicating that tissue-specific factors play a crucial role. Among the haplotypes studied, A1B1 exhibited the greatest reactivity on various stimuli. Electric mobility shift assay (EMSA) was performed to study whether the described polymorphic nucleotide sequences in the 5' region of the hCRH gene interfere with binding of nuclear proteins. A specific DNA protein complex was detected at position -2353 bp for the wild type sequence only, possibly interfering with a binding site for the activating transcription factor 6 (ATF6). Taken together, this is the first study to demonstrate that CRH promoter reactivity varies between the compound promoter alleles.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2006

[Evaluation of quantitative ultrasonometry of bone in singleton and multiple pregnancies].

OBJECTIVE: During pregnancy about 30 grams of calcium are transferred to a full-term neonate. The enormous demand for calcium can be regulated by compensatory mechanisms in the maternal metabolism such as elevated steroid hormone levels, increased intestinal absorption of dietary calcium, and renal conservation, but also by mobilization of calcium from the maternal skeleton. Therefore we have investigated whether a decrease in maternal bone mineral density (BMD) can be observed during pregnancy and whether it differs between singleton and twin pregnancies. METHODS: Quantitative ultrasonometry (QUS) was performed at the distal metaphysis of the phalanges (digits II - V). 54 singleton pregnancies and 6 twin pregnancies were longitudinally followed throughout pregnancy. In each trimester the amplitude-dependent speed of sound (AD-SOS) and the bone transmission time (BTT) were measured. RESULTS: In 54 singleton pregnancies significant decreases in AD-SOS of 1.9 % (p </= 0.001) and in BTT of 7.2 % (p < or = 0.001) were observed. In the corresponding twin pregnancies no significant decreases in AD-SOS (1.6 %) or BTT (6.6 %) could be detected. CONCLUSIONS: The results show that the compensatory mechanisms in maternal metabolism are not able to cover the fetal calcium demand and lead to a decrease in QUS parameters. In our pilot study due to the small number of twin pregnancies the decrease in QUS parameters did not reach statistical significance although the results seemed comparable to those of singleton pregnancies.

Bone Density↗
PubMed2005

The status of neck node metastases in breast cancer--loco-regional or distant?

Metastases to cervical lymph nodes do not exclusively derive from malignancies of the head and neck area. In the literature the region where distant metastases of breast carcinomas to the neck occur is exclusively named "supraclavicular". The system established by head and neck surgeons regarding neck node topography allows interdisciplinary management of patients with cervical lymph node metastases from breast cancer. Twelve patients suffering from breast cancer who presented with cervical masses have been examined. Most lymph node metastases were found in the posterior triangle of the neck and at the caudo-jugular level, but some metastases were even found in the upper jugular levels. The results presented show that neck node metastases of breast cancer are located superiorly to the supraclavicular region in more than 50% of the cases. According to the AJCC Staging System for Breast Cancer metastases located in the supraclavicular fossa are assessed as loco-regional metastases (N3c). Lymph node metastases situated above the supraclavicular region are not mentioned, but should be considered as distant metastases. This important question remains unanswered and deserves clarification in the current classification of the AJCC Staging System for Breast Cancer.

Adult↗
PubMed2005

[Acute dyspnoea].

Asthma, chronic obstructive pulmonary diseases, interstitial lung diseases and myocardial dysfunction are the leading diagnoses of patients with dyspnoea. Acute dyspnoea appears suddenly or within a few hours and is caused by a relatively limited number of conditions some of which can be life-threatening. Therefore, it is of utmost importance to identify the cause of dyspnoea immediately. Once found, the disorder is treated according to the guidelines for the underlying disease.

Acute Disease↗
PubMed2005

[Cardiovascular manifestations in rheumatoid arthritis].

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by a polyarticular joint inflammation which eventually leads to joint destruction and general disability. Besides these polyarticular manifestations, several systemic immune phenomena have been described. An increased mortality in RA patients is evident and is mainly caused by an increased cardiovascular risk. The correlation between disease activity and mortality highlighted the important role of the systemic inflammatory reaction in induction and progression of vascular damaging processes. Endothelial dysfunction and vascular inflammation are important, mechanisms in atherosclerosis and induced by conventional risk factors and systemic inflammation. It has been shown that the deleterious influence of conventional risk factors is aggravated by inflammatory mediators, mainly by pro-inflammatory cytokines. In addition, certain inflammatory mediators exert damaging effects to blood vessels. Especially CRP, merely considered as a risk indicating parameter in the past, has attracted remarkable attention. Also certain RA specific immune phenomena are of considerable proatherosclerotic potential. At least in part, they could be responsible for the excess mortality in RA patients. The newer TNFalpha blocking agents interfere with different mechanisms responsible for induction and perpetuation of atherosclerotic processes. Time will show whether they make a remarkable impact on the cardiovascular mortality in RA patients.

Arthritis, Rheumatoid↗
PubMed2005

[T cell-dependent monocyte activation, TNFalpha and apolipoprotein A-I in autoimmunity and inflammation].

Rheumatoid arthritis is characterized by a massive overproduction of monokines like TNFalpha, IL-6 and IL-1beta, which are predominantly produced by monocytes and macrophages. To date, the exact mechanisms of monocyte/macrophage activation have not been fully elucidated. One possible mechanism is their cell contact-dependent activation by activated T cells. The direct cell contact of monocytes/macrophages and T cells leads to an increased production of pro-inflammatory cytokines such as TNFalpha and IL-1beta. Stringent control of this mechanism by inhibitory factors appears mandatory under physiological conditions in order to avoid systemic cytokine release syndromes. The presence of inhibitory factors in the serum could represent such a mechanism. In healthy donors, apolipoprotein A-I was identified as such an inhibitory serum protein. In patients with rheumatoid arthritis, apolipoprotein A-I is found in decreased concentrations, possibly due to its role as a negative acute phase protein. The role of this and other inhibitory serum molecules are discussed.

Animals↗
PubMed2005

[T-lymphocytes--do they control rheumatic immune responses?].

T cells, in particular CD4(+) T cells, have been implicated in mediating many aspects of rheumatoid inflammation. In rheumatoid arthritis (RA), CD4(+) T cells display various functional abnormalities in the synovium as well as in the peripheral circulation. Current evidence suggests, however, that the role of CD4(+) T cells in the development of rheumatoid inflammation exceeds that of activated pro-inflammatory effector T cells that drive the chronic autoimmune response. Subsets of CD4(+) T cells with regulatory capacity, such as CD25(+) Tregs, have been identified in mice and man, and recent observations suggest that in RA, the function of these regulatory T cells is severely impaired. Thus, in RA, defective regulatory immune mechanisms might allow the breakdown of peripheral tolerance, following which the detrimental CD4(+) T-cell-driven immune response evolves and proceeds to chronic inflammation. Here, we review the functional abnormalities and the contribution of different T-cell subsets to rheumatoid inflammation.

Animals↗
PubMed2005

A phase II study of paclitaxel, carboplatin, and gemcitabine in previously untreated patients with epithelial ovarian cancer FIGO stage IC-IV (AGO-OVAR protocol OVAR-8).

PURPOSE: A multicenter, nonrandomized, phase II study was initiated to evaluate the tolerability, toxicity, and activity of paclitaxel, carboplatin, and gemcitabine combination in previously untreated ovarian cancer. PATIENTS AND METHODS: Chemonaive patients who had radical debulking surgery for primary epithelial ovarian cancer International Federation of Gynecology and Obstetrics (FIGO) IC-IV received sequentially paclitaxel 175 mg/m(2), carboplatin AUC 5, and gemcitabine 800 mg/m(2) on day 1 and gemcitabine 800 mg/m(2) on day 8, every 3 weeks. RESULTS: From October 2001 to July 2002, 55 patients were treated and evaluated. Main toxicities were hematological with NCI-CTC grade 3/4 anemia 12.7%, leukopenia 70.9%, neutropenia 76.3%, and thrombocytopenia 45.5. However, febrile neutropenia occurred only in 1.8%. Grade 3/4 nonhematological toxicities were rare and occurred in less than 10% of patients. Toxicity-induced treatment delays occurred in 3.1% of cycles and resulted in early treatment cessation in four patients. Dose intensity reached 90.8% for carboplatin and paclitaxel, and 73.3% for gemcitabine. Objective response was observed in 10 of 14 patients with measurable disease. CONCLUSIONS: The triplet combination of paclitaxel-carboplatin-gemcitabine is feasible and active, with manageable hematological toxicity and no unexpected nonhematological toxicity. This regimen has proceeded to phase III evaluation.

Adult↗
PubMed2005

[Mammographic breast density and breast cancer risk during HRT].

Higher breast density leads to a higher risk of breast-cancer coming along with a reduced sensitivity of mammography, the most important method for early diagnosis of breast cancer. HRT leads to an increase in breast density in up to (1/3) of treated women. Combined regimes of estrogen-progestin show a stronger influence than estrogen only. Changes of breast density appear almost entirely within the first year of administration and seem to be reversible after suspension of treatment within a few weeks. A possible solution of the dilemma is to perform mammography in asymptomatic premenopausal women during the first half of the menstrual cycle. In women with increased breast density using HRT it is recommended to modify the combination of hormones, change the application mode, or suspend HRT for a short period of 3 weeks prior to mammography. In symptomatic women with dense breasts, additive breast ultrasound is strongly recommended to reduce the otherwise high rate of missed breast cancers.

Breast Neoplasms↗