Biomedical subjects

Ulla Derhaschnig

Publications and source records attributed to Ulla Derhaschnig.

11 recordsLinked to original sources

PubMed2003

Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) has minimal effect on markers of coagulation, fibrinolysis, and inflammation in acute human endotoxemia.

Inflammatory and procoagulant host responses are closely related in sepsis. The protein C pathway serves as a regulatory pathway with anti-inflammatory and anticoagulant properties. Recently, recombinant human activated protein C (rhAPC) was shown to reduce mortality in severe sepsis. Nevertheless, the effects of rhAPC in humans are still ill defined. The infusion of low endotoxin doses into humans provides a standardized model to study inflammatory and hemostatic mechanisms. Thus, we investigated whether rhAPC acts as an anticoagulant or anti-inflammatory drug in human endotoxemia. There were 24 volunteers randomized to receive either 24 microg/kg per hour rhAPC or placebo intravenously for 8 hours. Lipopolysaccharide (LPS, 2 ng/kg) was administered 2 hours after starting the infusions. rhAPC decreased basal tissue factor (TF)-mRNA expression, and thrombin formation and action. In contrast, rhAPC did not significantly blunt LPS-induced thrombin generation. Consistently, rhAPC did not reduce LPS-induced levels of TF-mRNA or D-dimer and had no effect on fibrinolytic activity or inflammation. Finally, endogenous APC formation was enhanced during endotoxemia and appeared to be associated with inflammation rather than thrombin formation. In conclusion, even low-grade endotoxemia induces significant protein C activation. Infusion of rhAPC decreases "spontaneous" activation of coagulation but does not blunt LPS-induced, TF-mediated coagulation in healthy volunteers, which is in contrast to a number of anticoagulants.

Acute Disease↗

PubMed2003

Is fasting blood glucose a reliable parameter for screening for diabetes in hypertension?

BACKGROUND: The aim of this study was to evaluate the sensitivity and specificity of a combination of fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA(1c)) for screening for diabetes in hypertensive patients. The oral glucose tolerance test (OGTT) served as a gold standard for the detection of diabetes. METHODS: The cross-sectional study was performed in the Hypertension Unit of the Department of Emergency Medicine in the General Hospital of Vienna between January 1999 and July 2001. The FPG, HbA(1c), and OGTT were performed in 152 hypertensive patients (77 male and 75 female) to identify those individuals with diabetes. RESULTS: A total of 33 patients were identified as diabetic based on the results of the OGTT. Diabetes was detected in 25 (16%) of 152 patients using an FPG > or =7.0 mmol/L. In addition, HbA(1c) was measured in the remaining 127 (84%) patients with an FPG <7.0 mmol/L. In these patients HbA(1c) > or =6.1% showed a sensitivity of 100% and a specificity of 75%. Cost analysis of both approaches (FPG + HbA(1c) versus OGTT in all patients) demonstrated a cost sparing effect of 31.03 $/patient (31.66$/patient) in favor of the combined use of FPG and HbA(1c). CONCLUSION: The combination of FPG and HbA(1c) is a reasonable alternative to the generally recommended OGTT for the screening of diabetes, as diabetes was correctly diagnosed in all patients by this stepwise procedure.

Aged↗

PubMed2003

Levels of adhesion molecules do not decrease after 3 months of statin therapy in moderate hypercholesterolaemia.

Studies in animals and humans indicate a pivotal role for adhesion molecules (AMs) in the pathogenesis of atherosclerosis. Whereas an association between hypercholesterolaemia and AM expression has been suggested, it is unclear whether lowering cholesterol decreases AM expression and release. We compared the effects of a 3-month treatment with standard doses of three different statins (atorvastatin, simvastatin and pravastatin) on plasma levels of circulating AM (cAM) in 75 hypercholesterolaemic patients in a randomized clinical trial. Plasma levels of circulating (c)E-selectin, circulating intercellular adhesion molecule-1 (cICAM-1) and circulating vascular cell adhesion molecule-1 (cVCAM-1) were measured before and after 3 months of therapy. None of the statins lowered plasma cAM levels and pooled analyses of all patients showed a 1.7% [95% confidence interval (CI), -1.4-4.9%] increase in cE-selectin, a 2.1% (95% CI, -0.2-4.4%) increase in cICAM-1, and a 2.7% (95% CI, -0.6-6.1%) increase in cVCAM-1 levels. cAM levels did not decrease, even in patients with a >50% decrease ( n =19) in low-density lipoprotein cholesterol levels. This study provides strong evidence that 3 months of therapy with three different statins does not decrease cAM levels, despite normalization of cholesterol levels, and a minor decrease in C-reactive protein levels in patients with moderate hypercholesterolaemia.

Adult↗

PubMed2003

Endotoxaemia modulates Toll-like receptors on leucocytes in humans.

The modulation of Toll-like receptors (TLR) 1, 2 and 4 was studied during experimental human endotoxaemia. Healthy volunteers received 2 ng/kg of lipopolysaccharide (LPS) endotoxin (n = 10). TLR1, 2 and 4 expression occurred on monocytes and neutrophils, with monocytes expressing higher baseline levels of TLR2. LPS infusion downmodulated TLR4 expression on neutrophils, with maximal downregulation occurring at 24 h (-62% from baseline; P < 0.03 versus baseline). Monocyte TLRs were upregulated in vivo (TLR1 and 2), and in vitro (TLR1, 2 and 4) 8 h after LPS bolus (P < 0.05 versus baseline). Therefore, neutrophils and monocytes differentially express surface TLRs, and endotoxaemia differentially regulates TLR expression.

Adult↗

PubMed2003

Factors influencing the accuracy of oscillometric blood pressure measurement in critically ill patients.

OBJECTIVE: Comparison of oscillometric blood pressure measurement with two different devices (M3000A using a new algorithm and M1008A using an established algorithm, both Hewlett Packard) and evaluation of current recommendations concerning the relation between cuff size and upper arm circumference in critically ill patients. DESIGN: Prospective data collection. SETTING: Emergency department in a 2000-bed inner-city hospital. PATIENTS: A total of 30 patients categorized into three groups according to their upper arm circumference (I, 18-25 cm; II, 25.1-33 cm; III, 33.1-47.5 cm) were enrolled in the study protocol. INTERVENTIONS In each patient, two noninvasive blood pressure devices with three different cuff sizes were used to perform oscillometric blood pressure measurement. Invasive mean arterial blood pressure measurement was done by cannulation of the radial artery. MEASUREMENT AND MAIN RESULTS: Overall, 1,011 pairs of simultaneous oscillometric and invasive blood pressure measurements were collected in 30 patients (group I, n = 10; group II, n = 10; group III, n = 10). The overall discrepancy between both methods with the M3000A was -2.4 +/- 11.8 mm Hg (p <.0001) and, with the M1008A, -5.3 +/- 11.6 mm Hg (p <.0001) if the recommended cuff size according to the upper arm circumference was used (352 measurements). If smaller cuff sizes than recommended were used (308 measurements performed in group II and III), the overall discrepancy between both methods with the M3000A was 1.3 +/- 13.4 mm Hg (p <.024) and, with the M1008A, -2.3 +/- 11.5 mm Hg (p <.0001). CONCLUSION: The new algorithm reduced the overall bias of the oscillometric method but still showed a significant discrepancy between both methods of blood pressure measurement, primarily due to the mismatch between upper arm circumference and cuff size. The improvement of the algorithm alone could not result in a sufficient improvement of oscillometric blood pressure measurement. A reevaluation of the recommendations concerning the relation between upper arm circumference and cuff size are urgently required if oscillometric blood pressure measurement should become a reasonable alternative to intra-arterial blood pressure measurement in critically ill patients.

Adult↗

PubMed2003

Evaluation of antiinflammatory and antiadhesive effects of heparins in human endotoxemia.

OBJECTIVE: Cytokines and adhesion molecules have a decisive role in the development of early inflammatory response as well as the late sequelae of sepsis. Because L-selectin-deficient mice are protected from lethal endotoxemia, blockade of L-selectin may provide a useful therapeutic option in human sepsis. Heparin has immunomodulatory properties and effectively inhibits L- and P-selectin binding in vitro. We therefore investigated whether clinically applied doses of unfractionated or low-molecular-weight heparin affect early inflammatory response in human endotoxemia. DESIGN: The study was randomized, double-blinded, placebo-controlled, in three parallel groups consisting of 30 healthy male volunteers. SETTING: University medical center. INTERVENTIONS: All subjects received a 2-ng/kg intravenous bolus of lipopolysaccharide and 10 mins later unfractionated heparin, low-molecular-weight heparin, or placebo as bolus primed continuous infusion for 6 hrs. MEASUREMENTS AND MAIN RESULTS: Lipopolysaccharide infusion induced similar increases of tumor necrosis factor-alpha, interleukin-6, interleukin-8, C-reactive protein, and soluble E-selectin levels in all treatment groups. CD11b expression increased by approximately 400%, but L-selectin decreased by 41% in the placebo arm 6 hrs after lipopolysaccharide infusion. Interestingly, both heparins (in particular unfractionated heparin) decreased L-selectin down-regulation as compared with placebo. Similarly, the decrease in lymphocyte counts was significantly less in the unfractionated heparin group during the first 24 hrs (p <.05 vs. placebo) CONCLUSIONS: Heparins displayed little effects on cytokine production and endothelial cell activation in endotoxemia. Of note, however, unfractionated heparin reduced L-selectin down-regulation and lymphocytopenia. These could present novel mechanisms of action of unfractionated heparin.

Adult↗

PubMed2002

Increased levels of transforming growth factor-beta1 in essential hypertension.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that has been linked to vascular remodeling processes, myocardial hypertrophy, and renal fibrosis. Recently a correlation between serum levels of TGF-beta1 and blood pressure (BP) levels in patients with end-stage renal disease was shown. In addition, it is not clear whether TGF-beta1 is a causative factor in the pathogenesis of essential hypertension and associated with hypertensive target organ damage (TOD). METHODS: Using a TGF-beta1-specific sandwich ELISA, we compared plasma levels of active and total TGF-beta1 of 30 normotensive persons and 85 patients with essential hypertension with and without TOD, as measured by microalbuminuria or left ventricular hypertrophy. RESULTS: Active and total TGF-beta1 levels were significantly higher in plasma of patients with essential hypertension than in normotensive controls (P < .05 and P < .01, respectively). However, neither active nor total TGF-beta1 correlated with systolic or diastolic BP (R2 < 0.14 for all parameters). Levels of active and total TGF-beta1 were significantly higher in hypertensive patients with than without TOD (P < .05). CONCLUSIONS: Active and latent TGF-beta1 levels are markedly increased in plasma of hypertensive patients. We assume that TGF-beta1 contributes substantially to the development of TOD in essential hypertension, independent of BP levels.

Blood Pressure↗

PubMed2002

Microalbumin measurement alone or calculation of the albumin/creatinine ratio for the screening of hypertension patients?

BACKGROUND: Spot urine sampling seems to be a reliable screening method for the detection of microalbuminuria in hypertensive patients. It remains unclear whether microalbumin measurement alone or calculation of the albumin/creatinine ratio (ACR) are more reliable for the detection of microalbuminuria in non-selected hypertensive patients. METHODS: Following collection of a spot, midstream urine sample, urine was collected for 24 h for the measurement of microalbumin in 264 hypertensive patients. We compared microalbumin concentration in the spot urine with microalbumin measured in the 24-h urine sample and examined the utility of the ACR in evaluating microalbuminuria in hypertensive patients. Pathologic microalbuminuria was assumed when the microalbumin concentration exceeded 30 mg/l in the 24-h urine sample. Diagnostic performance is expressed in terms of specificity, sensitivity, positive (PPV) and negative predictive value (NPV), and area under receiver operating characteristics curve (AUC). RESULTS: A total of 47 samples (17.8%) showed pathologic microalbuminuria in the 24-h urine sample. The diagnostic performance expressed as AUC was 0.94 (95% CI 0.90-0.98) for microalbumin measurement alone and 0.94 (95% CI 0.89-0.97) for ACR. The PPV and NPV were 44.2 and 97.9% for microalbumin measurement alone. ACR revealed a PPV of 29.3% and a NPV of 96.2% for males and 42.9 and 98% for females, if a cut-off value of 2.5 mg/mmol for males and of 4.0 mg/mmol for females was used. CONCLUSIONS: The ACR did not provide any advantage compared with microalbumin measurement alone, but requires an additional determination of creatinine and the use of gender-specific cut-off values. Therefore, measurement of microalbuminuria alone in the spot urine sample is more convenient in daily clinical practice and should be used as the screening method for hypertensive patients.

Adult↗

PubMed2002

Angiotensin converting enzyme DD genotype is associated with hypertensive crisis.

OBJECTIVE: The genetic background of hypertensive crisis is unknown. We examined the association of polymorphisms in genes involved in the renin-angiotensin-aldosterone-system with hypertensive crisis. DESIGN: Population-based case-control study. SETTING: Emergency department at a tertiary care university hospital. PATIENTS: A total of 182 patients with essential hypertension who were admitted to an emergency department for treatment of hypertensive crisis and 182 age- and sex-matched healthy individuals. INTERVENTIONS: None. MEASUREMENTS: Analysis of polymorphisms in genes coding for angiotensinogen (AJT 704T-->C), angiotensin II receptor 1 (AGTR1 1166A-->C), renin (REN 2646G-->A), renin-binding protein (RENBP 61T-->C), alpha-adducin (ADD1 1378G-->T), beta-2-adrenergic receptor (ADRB2 46A-->G, 79C-->G), and angiotensin I converting enzyme (ACE I/D) was performed by polymerase chain reaction and restriction fragment length polymorphism analysis. MAIN RESULTS Among patients, the ACE I/D polymorphism showed a deviation from Hardy-Weinberg equilibrium (p =.01). In controls, all polymorphisms were in the Hardy-Weinberg equilibrium. The frequency of the DD genotype was increased in patients (n = 70, 38.5%) vs. controls (n = 51; 28.0%;p =.03; odds ratio, 1.61; 95% confidence interval, 1.03-2.50), which was due to the DD genotype in 40 male patients (44%) vs. 23 in male controls (25.3%;p =.004; odds ratio, 3.48; 95% confidence interval, 1.47-8.30). There were no differences in genotype distributions among other polymorphisms. CONCLUSION: We demonstrate a possible association of the DD genotype with hypertensive crisis in men.

Angiotensinogen↗

PubMed2002

Classification of blood pressure levels by ambulatory blood pressure in hypertension.

Whereas clinic blood pressure (CBP) above normality is divided into stages, no corresponding classifications are available for 24-hour ambulatory blood pressure (ABP). We conducted a study (1) to define stages of hypertension by ABP corresponding to CBP stages and (2) to evaluate if these stages have prognostic impact similar to CBP stages. Seven hundred thirty-six hypertensive patients were included. Mean systolic blood pressure was 149+/-15.2/87+/-8.6 mm Hg for CBP and 135+/-13/79+/-9.7 mm Hg for ABP. The mean bias between both methods was -13.3 mm Hg (95% CI, -14.3 to -12.2; 1.96xSD limits of agreement, 15.7 to -42.3) and -7.3 mm Hg (95% CI, -7.9 to -6.6; 1.96xSD limits of agreement, 9.8 to -24.3) for systolic and diastolic blood pressure (P>0.0001 for both), respectively. Classification of hypertension by ABP revealed lower cutoff values for the different stages of hypertension compared with the corresponding cutoff values for CBP (CBP versus ABP: 140/90 versus 132/81 mm Hg; 160/100 versus 140/88 mm Hg; 180/110 versus 148/94 mm Hg, P<0.001). Overall, 82 (11.1%) patients had nonfatal clinical cardiovascular events and 9 (1.2%) patients died of a cardiovascular cause during follow-up. The distribution of cardiovascular events was significantly associated with increasing ABP value (P<0.006). Staging of hypertension by ABP may facilitate the use of this method in daily clinical practice, as ABP can now be used not only to confirm the diagnosis of hypertension but also to assess the severity and prognosis of hypertensive disease.

Age Distribution↗

PubMed2002

Evaluation of coagulation markers for early diagnosis of acute coronary syndromes in the emergency room.

BACKGROUND: Diagnosis of acute coronary syndromes (ACS) is a major challenge for emergency physicians. Because soluble fibrin (sF) has been suggested as a potential early marker of impending myocardial ischemia, we were interested whether a sF bedside test could help in early identification of patients with ACS in the emergency department. METHODS: We evaluated plasma coagulation markers, including a newly developed sF bedside test, prothrombin fragment (F(1+2)), sF, and D-dimer, in a cross-sectional trial with 184 patients suggestive of ACS. RESULTS: Whereas 76% (13 of 17) of patients with unstable angina pectoris (UAP) had a positive sF bedside test, only 10 of 33 patients (30%) with non-ST-segment-elevation myocardial infarction and 10 of 44 patients (23%) with ST-elevation myocardial infarction tested positive. Three percent of controls (1 of 33) and 11% of patients (6 of 57) with preexisting stable angina had a positive sF bedside test (P <0.001 for noncardiac chest pain vs ACS), yielding an overall specificity of 92% and a sensitivity of 35%. The sensitivity of the established coagulation markers was significantly less to detect ACS (11% for F(1+2), 20% for thrombus precursor protein, and 18% for D-dimer; P <0.02 vs sF bedside test). The sF bedside test presented the earliest objective indicator of impending myocardial damage in the majority (10 of 13) of ACS patients with a normal or nondiagnostic electrocardiogram (ECG). CONCLUSIONS: A sF bedside test offers a specific tool for early identification of patients with ACS in an emergency department setting, although its sensitivity seems sufficient only for the early identification of patients with UAP. A sF bedside test could be useful, particularly in UAP patients with a nondiagnostic ECG.

Acute Disease↗