Christine Scholten

Tissue Expression and Serum Levels of HER-2/neu in Patients with Breast Cancer

We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.

Persistent functional and social benefit 5 years after a multidisciplinary arthritis training program

OBJECTIVE To assess the sustainable benefits of a professional, multidisciplinary training program for patients with rheumatoid arthritis. DESIGN Two studies with different observation periods. Study I was a prospective, randomized trial for 1 year. Study II was a noncontrolled observation over 5 years. SETTING The 9-day program for eight patient groups encompassed a multidisciplinary cooperation between rheumatologists, orthopedists, physicotherapists, psychologists and social workers. PATIENTS Sixty-eight consecutive patients with rheumatoid arthritis participated in an arthritis training program either immediately after enrollment in the program or after 1 year. INTERVENTIONS The program covered the following fields: pathogenesis of rheumatoid arthritis, drug therapy, physicotherapy, practical exercise in remedial gymnastics, use of joint protection devices, orthopedic perspectives, psychological counseling, dietetics, information about unproven cures and social assistance. MAIN OUTCOME MEASURES Clinical outcome was assessed by self-report questionnaires: (1) Stanford Health Assessment Questionnaire, (2) Freiburg Questionnaire of Coping with Illness, (3) Beck Depression Inventory, and (4) a 21-point scale to evaluate cognitive-behavioral and environmental impact. RESULTS A significant and persistent improvement of all investigated parameters was demonstrated in the 1-year controlled trial. Between the end-point of the 1-year study and the 5-year evaluation, this improvement increased even more for functional status and coping with illness, whereas depression returned to baseline values. These effects were seen even without reinforcement of the training. CONCLUSION A professional, multidisciplinary approach to educate patients with rheumatoid arthritis leads to a significant and sustained improvement of the clinical outcome and is an approach that should be established as a part of conventional therapy.

Moderate patient-prosthesis mismatch after valve replacement for severe aortic stenosis has no impact on short-term and long-term mortality

Background: The importance of moderate patient-prosthesis mismatch (PPM) for the prognosis of patients who undergo aortic valve replacement is unclear. Methods: The presence of PPM was assessed in 361 consecutive patients undergoing valve replacement for isolated severe aortic stenosis and related to perioperative and postoperative mortality. Indexed effective orifice areas (EOAi) were estimated for each type and size of prosthesis. Results: Using the previously proposed cut-off of EOAi ⩽0.8 cm2/m2, PPM was present in 54% of patients. Patients were followed for 4.1 (2.0) years. Survival tended to be slightly, but insignificantly, worse in the group with PPM (1-year, 3-year and 5-year survival 89%, 86% and 76% vs 92%, 88% and 82%; p = 0.21). However, patients with PPM were also older (p<0.0001), more often female (p<0.0001), more symptomatic (p = 0.001), more often had coronary artery disease (p = 0.04), triple vessel disease (p = 0.03) and hypertension (p = 0.01) and presented with a higher EuroSCORE (p<0.0001). By multivariate analysis only EuroSCORE and diabetes but not PPM were independent predictors of survival. Conclusions: Moderate PPM is a frequent finding after aortic valve replacement. In our patient population it had no impact on short-term and long-term survival. It may therefore not be justified to recommend complex surgical interventions to avoid moderate PPM in patients undergoing aortic valve replacement for isolated severe aortic stenosis.

Effect of estrogen replacement therapy on natural killer cell activity in postmenopausal women

OBJECTIVE To evaluate the impact of menopause and estradiol substitution on natural killer cell activity. METHODS Natural killer cell activity and antibody-dependent cellular cytotoxicity were measured in peripheral blood of 53 postmenopausal and 20 premenopausal women in an interval of 3 weeks. Postmenopausal patients were randomly assigned to receive either estradiol valerate (2 mg daily) orally (n = 18), estradiol (50 micrograms/24 h) transcutaneously (n = 18) or no substitution (n = 17), and the testing was repeated 3 weeks later. RESULTS Natural killer cell activity but not antibody-dependent cellular cytotoxicity was significantly (P < 0.01) higher in unsubstituted postmenopausal compared to premenopausal subjects. Natural killer cell activity decreased both in orally and transcutaneously estradiol-treated patients (mean [S.D.] before vs. after 3 weeks; oral: 60.8 [9.2]% vs. 52.8 [8.2]% P < 0.01; transcutaneous: 61.5 [10.6]% vs. 54.3 [9.1]% P < 0.01; no substitution: 60.6 [10.6]% vs. 59.3 [8.9]% P > 0.1), whereas antibody-dependent cellular cytotoxicity showed no changes. The addition of 0.1 to 10 ng/ml estradiol to peripheral blood mononuclear cells of untreated postmenopausal women in vitro had no influence upon natural killer cell activity. CONCLUSION Postmenopausal women receiving no estrogen replacement exhibited an increased natural killer cell activity which decreased during estrogen substitution.

NT-proBNP as a means of triage for the risk of hospitalisation in primary care

Background: In primary care, identification of patients who are at risk of major adverse events is of great importance. At the same time identifying individuals who are at very low risk and do not need further diagnostic workup and therapy is also important and may help to correctly allocate scarce healthcare resources. Aim: This study evaluated amino-terminal pro B-natriuretic peptide (NT-proBNP) as a risk marker in primary care patients with hypertension, diabetes, clinically suspected heart failure (HF), history of coronary artery disease or myocardial infarction. Methods and results: A prospective observational study was conducted in 1203 primary care patients. The primary endpoint, time to all-cause hospitalisation, was reached in 282 (24%) individuals within 12 months. Of all variables analysed, only NT-proBNP (HR 1.001 [1.000–1.001], p < 0.001) and age (HR 1.018 [1.007–1.028], p = 0.001) were of independent predictive value in a stepwise Cox regression analysis regarding all-cause hospitalisation. Neither systolic dysfunction nor signs and symptoms of HF added independent information to predict outcome. The negative predictive value (NPV) increased depending on the specificity of the endpoint (NPV was 86% for all-cause, 98% for cardiac and 100% for HF-related hospitalisation for 125 pg/ml). Positive predictive value and NPV were superior for NT-proBNP compared to clinical signs and symptoms of HF at every cut-point between 100 and 500 pg/ml. Conclusion: NT-proBNP levels predicted clinical events in primary care patients at risk. NPVs were excellent in this high risk population, proving NT-proBNP measurement a safe diagnostic tool.

Was geschieht im Krankenhaus

In Osterreich wurden im Jahr 1992 etwa 30.000 Neuerkrankungen an Krebs gemeldet. Bei Mannern trat am haufigsten Prostatakrebs (15,4%), Darmkrebs (15, 2%) und Lungenkrebs (14, 1%) auf. Bei Frauen lag Brustkrebs (22, 7 %) an der Spitze, zweithaufigste Krebsart war ebenfalls der Darmkrebs (13%), an dritter Stelle kam bei Frauen der Hautkrebs (10, 8%).