B-type natriuretic peptide and wall stress in dilated human heart

Background Although B-type natriuretic peptide (BNP) is used as complimentary diagnostic tool in patients with unknown thoracic disorders, many other factors appear to trigger its release. In particular, it remains unresolved to what extent cellular stretch or wall stress of the whole heart contributes to enhanced serum BNP concentration. Wall stress cannot be determined directly, but has to be calculated from wall volume, cavity volume and intraventricular pressure of the heart. The hypothesis was, therefore, addressed that wall stress as determined by cardiac magnetic resonance imaging (CMR) is the major determinant of serum BNP in patients with a varying degree of left ventricular dilatation or dysfunction (LVD). Methods A thick-walled sphere model based on volumetric analysis of the LV using CMR was compared with an echocardiography-based approach to calculate LV wall stress in 39 patients with LVD and 21 controls. Serum BNP was used as in vivo marker of a putatively raised wall stress. Nomograms of isostress lines were established to assess the extent of load reduction that is necessary to restore normal wall stress and related biochemical events. Results Both enddiastolic and endsystolic LV wall stress were correlated with the enddiastolic LV volume (r = 0.54, P < 0.001; r = 0.81, P < 0.001). LV enddiastolic wall stress was related to pulmonary pressure (capillary: r = 0.69, P < 0.001; artery: r = 0.67, P < 0.001). Although LV growth was correlated with the enddiastolic and endsystolic volume (r = 0.73, P < 0.001; r = 0.70, P < 0.001), patients with LVD exhibited increased LV wall stress indicating an inadequately enhanced LV growth. Both enddiastolic (P < 0.05) and endsystolic (P < 0.01) wall stress were increased in patients with increased BNP. In turn, BNP concentration was elevated in individuals with increased enddiastolic wall stress (>8 kPa: 587 +/- 648 pg/ml, P < 0.05; >12 kPa: 715 +/- 661 pg/ml, P < 0.001; normal < or =4 kPa: 124 +/- 203 pg/ml). Analysis of variance revealed LV enddiastolic wall stress as the only independent hemodynamic parameter influencing BNP (P < 0.01). Using nomograms with "isostress" curves, the extent of load reduction required for restoring normal LV wall stress was assessed. Compared with the CMR-based volumetric analysis for wall stress calculation, the echocardiography based approach underestimated LV wall stress particularly of dilated hearts. Conclusions In patients with LVD, serum BNP was increased over the whole range of stress values which were the only hemodynamic predictors. Cellular stretch appears to be a major trigger for BNP release. Biochemical mechanisms need to be explored which appear to operate over this wide range of wall stress values. It is concluded that the diagnostic use of BNP should primarily be directed to assess ventricular wall stress rather than the extent of functional ventricular impairment in LVD.     

A personal computer-based system for online monitoring of neurologic intensive care patients]

In the management of neurological intensive care patients with an intracranial space-consuming process the measurement and recording of intracranial pressure together with arterial blood pressure is of special interest. These parameters can be used to monitor the treatment of brain edema and hypertension. Intracranial pressure measurement is also important in the diagnosis of the various subtypes of hydrocephalus. Not only the absolute figures, but also the recognition of specific pressure-patterns is of particular clinical and scientific interest. This new, easily installed and inexpensive system comprises a PC and a conventional monitor, which are connected by an AD-conversion card. Our software, specially developed for this system demonstrates, stores and prints the online-course and the trend of the measurements. In addition it is also possible to view the online-course of conspicuous parts of the trend curve retrospectively and to use these values for statistical analyses. Object-orientated software development techniques were used for flexible graphic output on the screen, printer or to a file. Though developed for this specific purpose, this system is also suitable for recording continuous, longer-term measurements in general.     

Correcting for finite spatial scales of self-similarity when calculating fractal dimensions of real-world structures

Fractal geometry is a potentially valuable tool for quantitatively characterizing complex structures. The fractal dimension (D) can be used as a simple, single index for summarizing properties of real and abstract structures in space and time. Applications in the fields of biology and ecology range from neurobiology to plant architecture, landscape structure, taxonomy and species diversity. However, methods to estimate the D have often been applied in an uncritical manner, violating assumptions about the nature of fractal structures. The most common error involves ignoring the fact that ideal, i.e. infinitely nested, fractal structures exhibit self-similarity over any range of scales. Unlike ideal fractals, real-world structures exhibit self-similarity only over a finite range of scales.Here we present a new technique for quantitatively determining the scales over which real-world structures show statistical self-similarity. The new technique uses a combination of curve-fitting and tests of curvilinearity of residuals to identify the largest range of contiguous scales that exhibit statistical self-similarity. Consequently, we estimate D only over the statistically identified region of self-similarity and introduce the finite scale- corrected dimension (FSCD). We demonstrate the use of this method in two steps. First, using mathematical fractal curves with known but variable spatial scales of self-similarity (achieved by varying the iteration level used for creating the curves), we demonstrate that our method can reliably quantify the spatial scales of self-similarity. This technique therefore allows accurate empirical quantification of theoretical Ds. Secondly, we apply the technique to digital images of the rhizome systems of goldenrod (Solidago altissima). The technique significantly reduced variations in estimated fractal dimensions arising from variations in the method of preparing digital images. Overall, the revised method has the potential to significantly improve repeatability and reliability for deriving fractal dimensions of real-world branching structures.     

Possible role of pheromones in modifying drug response in the mouse

Significant differences in the duration of response of Swiss Webster mice to hexobarbital and zoxazolamine are obtained, within siex, depending upon whether group caged animals are housed in rooms with mice of the same sex or with mice of the opposite sex. As there is no physical contact between animals, these findings suggest that pheromones or other moes of sexual communication may be operative.     

Spontaneous regression of cancer: New insights

Suppression of oncogene expression and of host- or tumour-expressed growth factors and receptors may precipitate spontaneous regression or dormancy in human cancer. Loss of oncogenes necessary for progressive proliferation can lead to differentiation changes. Both natural factors and chemical agents can trigger such a change, and of the naturally occurring agents, growth factors and immunological factors have been most studied. We may find new clues to biological methods of prolonging arrest of cancer, by looking for cytogenetic abnormalities, alterations in oncogene expression and immunocytological composition, in patients showing prolonged dormancy of cancer.     

Frequency of anemia in Rostock students]

For the purpose of determining the frequency of anaemia a check-up was made in 735 students (498 females, 237 males) at an age of at least 19 years at the beginning of their university studies. 9.4% of them had subnormal haemoglobin values. 91.3% of them were female students. A comparison between the test persons with a decrease of haemoglobin values and those without it on the one hand and data gathered from the students' health certificate on the other hand, revealed no ensured aetiologic connection. Analyzing the state of health of that group with lowered Hb-values showed that more than half of them suffered from diseases (mostly infections) at the time, when the blood examination was made. A check-up made one year later resulted in a high percentage of normalized values. Comparisons taken from medical literature clearly indicate that the frequency of anaemia of this student population examined here is relatively low in total. From an organizational point of view, complete check-up examinations shoudl be carried out or induced for female students by the outpatient departments working at the institutions of higher learning because they provide better possibilities of covering them.     

Vascular smooth muscle cells direct extracellular dysregulation in aortic stiffening of hypertensive rats

Aortic stiffening is an independent risk factor that underlies cardiovascular morbidity in the elderly. We have previously shown that intrinsic mechanical properties of vascular smooth muscle cells (VSMCs) play a key role in aortic stiffening in both aging and hypertension. Here, we test the hypothesis that VSMCs also contribute to aortic stiffening through their extracellular effects. Aortic stiffening was confirmed in spontaneously hypertensive rats (SHRs) vs. Wistar‐Kyoto (WKY) rats in vivo by echocardiography and ex vivo by isometric force measurements in isolated de‐endothelized aortic vessel segments. Vascular smooth muscle cells were isolated from thoracic aorta and embedded in a collagen I matrix in an in vitro 3D model to form reconstituted vessels. Reconstituted vessel segments made with SHR VSMCs were significantly stiffer than vessels made with WKY VSMCs. SHR VSMCs in the reconstituted vessels exhibited different morphologies and diminished adaptability to stretch compared to WKY VSMCs, implying dual effects on both static and dynamic stiffness. SHR VSMCs increased the synthesis of collagen and induced collagen fibril disorganization in reconstituted vessels. Mechanistically, compared to WKY VSMCs, SHR VSMCs exhibited an increase in the levels of active integrin β1‐ and bone morphogenetic protein 1 (BMP1)‐mediated proteolytic cleavage of lysyl oxidase (LOX). These VSMC‐induced alterations in the SHR were attenuated by an inhibitor of serum response factor (SRF)/myocardin. Therefore, SHR VSMCs exhibit extracellular dysregulation through modulating integrin β1 and BMP1/LOX via SRF/myocardin signaling in aortic stiffening.