[Procalcitonin in the intensive care unit : Differential diagnostic and differential therapeutic possibilities]. / Prokalzitonin auf der Intensivstation : Differenzialdiagnose und Differenzialtherapie.

Procalcitonin (PCT) is formed in IL6-mediated, IL8-mediated, and TNFα-mediated systemic inflammation conditions, in multiple organs and structures of the body. In patients with sepsis, significantly increased PCT levels are found. The PCT levels are highly correlated with the severity of the illness, and decreased PCT levels under therapy correlates with a better prognosis. In the differential diagnosis, measuring the PCT level helps differentiate between bacterial and viral infections. Noninfectious inflammatory reactions can, however, show moderately increased PCT levels. Cut-off values depend on renal and hepatic function. A therapeutic algorithm using PCT levels could be used for determining duration of a course of antibiotics, which can reduce antibiotic usage. In this paper, the differential diagnostic and differential therapeutic possibilities of PCT levels for critically ill patients are discussed.

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin-treated rats.

AIM: Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo. METHODS: Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests. RESULTS: Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups. CONCLUSIONS: Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

Effects of selective and unselective endothelin-receptor antagonists on prostacyclin synthase gene expression in experimental pulmonary hypertension.

OBJECTIVE: Compared to the unselective endothelin (ET) receptor antagonist (Bosentan), superior effects of selective ET-A-receptor blockage (Ambrisentan) for the treatment of pulmonary hypertension (PH) are expected due to ET-B-receptor mediated beneficial effects. Our hypothesis was that treatment with Ambrisentan leads to an increase in prostacyclin synthase I (PGIS) expression compared to Bosentan. MATERIAL AND METHODS: To test this hypothesis, rats were treated with either monocrotaline (MCT) only, MCT+Ambrisentan or MCT+Bosentan. After 4 weeks, right ventricular systolic pressure (RVSP), pulmonary vascular remodelling and right ventricular hypertrophy (RV/(LV+S)) were measured. RESULTS: In MCT only treated animals, significantly greater expression of PGIS mRNA was found in the lungs compared to control animals, and this was confirmed by immunohistochemical analysis indicating increased staining of PGIS in the very small pulmonary arteries (17 % greater expression of PGIS mRNA in MCT versus control, p = 0.002; Remmele score (RS): 51 versus 102, p = 0.009). Treatment with Bosentan resulted in a significantly lower expression of PGIS mRNA compared to Ambrisentan and MCT only (7 % versus 18 %, p = 0.003 and 7 % versus 17 %, p = 0.004). This observation was also confirmed by immunohistochemical analysis (RS very small arteries: 45 versus 81, p = 0.003; RS small arteries: 45 versus 108, p = 0.014). No difference was observed in RVSP, RV/(LV+S) or pulmonary vascular remodelling between the two treatment groups (RVSP: 28 versus 39 mmHg, p = 0.189; RV/(LV+S) 0.46 versus 0.48, p = 0.818; medial area: 78.3 % versus 75.2 %, p = 0.823). CONCLUSIONS: Treatment with Bosentan leads to lower PGIS expression in pulmonary arteries compared to Ambrisentan, although the greater PGIS expression by Ambrisentan treatment had no benefical effect on pulmonary haemodynamics.

Impact of noninvasive home ventilation on long-term survival in chronic hypercapnic COPD: a prospective observational study.

AIMS: The long-term benefit from noninvasive ventilation (NIV) in chronic hypercapnic chronic obstructive pulmonary disease (COPD) remains uncertain. METHODS: Within a prospective observational design, we compared the long-term survival of 140 patients with severe persistent hypercapnic COPD (FEV(1) 28.7 +/- 8.7% predicted; PaCO(2) 60.1 +/- 9.2 mmHg) with (n = 99) or without (n = 41) NIV. End-point was all-cause mortality, determined up to 4 years by Kaplan-Meier analysis. Additionally, Cox's proportional hazards regression and stratification by risk factors was performed. Patients were characterised by anthropometric and functional parameters, comorbidities and medical therapy. RESULTS: Adherence in patients with NIV was high (88.9%), daily ventilator use being 6.4 +/- 2.6 h/day and inspiratory pressures 21.0 +/- 4.0 cmH(2)O. One- and 2-year survival rates were 87.7% and 71.8%, respectively, in patients with NIV vs. 56.7% and 42.0% in patients without NIV. Survival rates were significantly higher in patients with NIV compared to those without this therapy (p = 0.001; hazard ratio 0.380; 95% confidence interval 0.138-0.606). The difference between groups was still significant after adjustment for differences in baseline characteristics. Moreover, stratification by risk factors revealed beneficial effects, particularly in patients with high base excess (BE; > 8.9 mmol/l), low pH (< 7.41), FEV(1) (< 27.5%) haemoglobin (< 13.8 g/dl) or large hyperinflation (residual volume-to-total lung capacity > 189% predicted) upon inclusion (p < 0.05 each). CONCLUSION: In patients with severe chronic hypercapnic COPD receiving NIV at high inspiratory pressure levels and showing high adherence to this therapy, long-term survival was significantly higher than in non-ventilated patients. Patients displaying more severe disease according to known risk factors seemed to benefit most from long-term NIV.

Hemorrhagic shock primes the hepatic portal circulation for the vasoconstrictive effects of endothelin-1.

To test whether hemorrhagic shock and resuscitation (HSR) alters the vascular responsiveness of the portohepatic circulation to endothelins (ETs), we studied the macro- and microcirculatory effects of the preferential ET(A) receptor agonist ET-1 and of the selective ET(B) receptor agonist sarafotoxin 6c (S6c) after 1 h of hemorrhagic hypotension and 5 h of volume resuscitation in the isolated perfused rat liver ex vivo using portal pressure-flow relationships and epifluorescence microscopy. Although HSR did not cause major disturbances of hepatic perfusion per se, the response to ET-1 (0.5 x 10(-9) M) was enhanced, leading to greater increases in portal driving pressure, total portal resistance, and zero-flow pressures and more pronounced decreases in portal flow, sinusoidal diameters, and hepatic oxygen delivery compared with time-matched sham shock controls. In sharp contrast, the constrictive response to S6c (0.25 x 10(-9) M) remained unchanged. Thus HSR primes the portohepatic circulation for the vasoconstrictive effects of ET-1 but does not alter the effects of the ET(B) receptor agonist S6c. The enhanced sinusoidal response may contribute to the subsequent development of hepatic microcirculatory failure after secondary insults that are associated with increased generation of ET-1.

The influence of lymph node metastasis and ulceration of primary melanoma on germinal centers within draining lymph nodes: a histomorphometric study.

Microscopic counts and histoelectronic measurement of germinal centers in regional lymph nodes of melanoma patients showed a significant progressive increase in average number, as well as area, of germinal centers with occurrence of (adjacent) metastasis and presence of primary-tumor ulceration. The findings confirm in a quantitative manner the stage-dependent effect of progressive liberation of tumor antigen [10] on lymph node centers of humoral immune response.