Predicting perceived vulnerability for breast cancer among women with an average breast cancer risk

OBJECTIVES: The purpose of the present study was to investigate predictors of perceived vulnerability for breast cancer in women with an average risk for breast cancer. On the basis of empirical findings that suggested which variables might be associated with perceived vulnerability for breast cancer, we investigated whether knowledge of breast cancer risk factors, cancer worry, intrusions about breast cancer, optimism about not getting cancer and perceived health status have a predictive value for perceived breast cancer vulnerability. DESIGN: In a 3-step approach, we recruited 292 women from the general public in Germany who had neither a family history of breast cancer nor breast cancer themselves. After receiving an initial informational letter about study objectives, the women were interviewed by telephone and then asked to fill in a self-administered questionnaire. METHODS: We used structural equation modelling and hypothesized that each of the included variables has a direct influence on perceived vulnerability for breast cancer. RESULTS: We found a valid model with acceptable fit indices. Optimism about not getting cancer, intrusions about breast cancer and women's perceived health status explained 32% of the variance of perceived vulnerability for breast cancer. Cancer worry and knowledge about breast cancer did not influence perceived vulnerability for breast cancer. CONCLUSION: Perceived vulnerability for breast cancer is associated with health-related variables more than with knowledge about breast cancer risk factors.

Local targeting of malignant gliomas by the diffusible peptidic vector 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid-substance p

PURPOSE: Malignant glial brain tumors consistently overexpress neurokinin type 1 receptors. In classic seed-based brachytherapy, one to several rigid (125)I seeds are inserted, mainly for the treatment of small low-grade gliomas. The complex geometry of rapidly proliferating high-grade gliomas requires a diffusible system targeting tumor-associated surface structures to saturate the tumor, including its margins. EXPERIMENTAL DESIGN: We developed a new targeting vector by conjugating the chelator 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid to Arg(1) of substance P, generating a radiopharmaceutical with a molecular weight of 1,806 Da and an IC(50) of 0.88 +/- 0.34 nmol/L. Cell biological studies were done with glioblastoma cell lines. neurokinin type-1 receptor (NK1R) autoradiography was done with 58 tumor biopsies. For labeling, (90)Y was mostly used. To reduce the "cross-fire effect" in critically located tumors, (177)Lut and (213)Bi were used instead. In a pilot study, we assessed feasibility, biodistribution, and early and long-term toxicity following i.t. injection of radiolabeled 1,4,7,10-tetraazacyclododecane-1-glutaric acid-4,7,10-triacetic acid substance P in 14 glioblastoma and six glioma patients of WHO grades 2 to 3. RESULTS: Autoradiography disclosed overexpression of NK1R in 55 of 58 gliomas of WHO grades 2 to 4. Internalization of the peptidic vector was found to be specific. Clinically, the radiopharmeutical was distributed according to tumor geometry. Only transient toxicity was seen as symptomatic radiogenic edema in one patient (observation period, 7-66 months). Disease stabilization and/or improved neurologic status was observed in 13 of 20 patients. Secondary resection disclosed widespread radiation necrosis with improved demarcation. CONCLUSIONS: Targeted radiotherapy using diffusible peptidic vectors represents an innovative strategy for local control of malignant gliomas, which will be further assessed as a neoadjuvant approach.

Flow cytometry and FISH to measure the average length of telomeres (flow FISH)

Telomeres have emerged as crucial cellular elements in aging and various diseases including cancer. To measure the average length of telomere repeats in cells, we describe our protocols that use fluorescent in situ hybridization (FISH) with labeled peptide nucleic acid (PNA) probes specific for telomere repeats in combination with fluorescence measurements by flow cytometry (flow FISH). Flow FISH analysis can be performed using commercially available flow cytometers, and has the unique advantage over other methods for measuring telomere length of providing multi-parameter information on the length of telomere repeats in thousands of individual cells. The accuracy and reproducibility of the measurements is augmented by the automation of most pipetting (aspiration and dispensing) steps, and by including an internal standard (control cells) with a known telomere length in every tube. The basic protocol for the analysis of nucleated blood cells from 22 different individuals takes about 12 h spread over 2-3 days.

Prediction of hypertensive crisis based on average, variability and approximate entropy of 24-h ambulatory blood pressure monitoring

Approximate entropy (ApEn) of blood pressure (BP) can be easily measured based on software analysing 24-h ambulatory BP monitoring (ABPM), but the clinical value of this measure is unknown. In a prospective study we investigated whether ApEn of BP predicts, in addition to average and variability of BP, the risk of hypertensive crisis. In 57 patients with known hypertension we measured ApEn, average and variability of systolic and diastolic BP based on 24-h ABPM. Eight of these fifty-seven patients developed hypertensive crisis during follow-up (mean follow-up duration 726 days). In bivariate regression analysis, ApEn of systolic BP (P<0.01), average of systolic BP (P=0.02) and average of diastolic BP (P=0.03) were significant predictors of hypertensive crisis. The incidence rate ratio of hypertensive crisis was 14.0 (95% confidence interval (CI) 1.8, 631.5; P<0.01) for high ApEn of systolic BP as compared to low values. In multivariable regression analysis, ApEn of systolic (P=0.01) and average of diastolic BP (P<0.01) were independent predictors of hypertensive crisis. A combination of these two measures had a positive predictive value of 75%, and a negative predictive value of 91%, respectively. ApEn, combined with other measures of 24-h ABPM, is a potentially powerful predictor of hypertensive crisis. If confirmed in independent samples, these findings have major clinical implications since measures predicting the risk of hypertensive crisis define patients requiring intensive follow-up and intensified therapy.

Soft tissue profile changes following mandibular advancement and setback surgery an average of 12 years postoperatively

PURPOSE: The aim of this study was to assess long-term changes in position of soft tissue landmarks following mandibular advancement and setback surgery. MATERIALS AND METHODS: Twenty-seven patients (14 women, 13 men; mean age, 36 years) who had undergone either mandibular advancement (15 patients) or setback surgery (12 patients), were available for a long-term follow-up an average of 12 years postoperatively. In all of these cases, lateral cephalometric radiographs taken immediately before operation, at 1 week, 14 months, and 12 years postoperatively, were studied. RESULTS: During the 14 months postoperatively, soft tissue chin and mentolabial fold followed its underlying hard tissue in all patients. A continuous skeletal relapse was observable 12 years after mandibular advancement, but soft tissue chin moved more in an anterior direction. After mandibular setback, soft and hard tissue landmarks remained almost unchanged. Over the entire observation period, a thickening of soft tissue at pogonion was generally seen, and particularly a thickening of the whole chin in the setback group. All patients showed a significant lengthening and thinning of the upper lip. In all except 2 males, the patient's body weight increased markedly. CONCLUSION: In contrast to the immediate postoperative stage, soft tissue changes observed an average of 12 years after the primary operation do not directly follow the movements of the underlying skeletal structure. The soft tissue profile changes observed over such a long term seem to be influenced not only by the underlying skeletal structure but also by other factors such as weight gain and aging process.