PubMed Health⌕ Search

Biomedical subjects

Uwe Janssens

Publications and source records attributed to Uwe Janssens.

At least 19 recordsLinked to original sources
PubMed2007

Endotoxin hypersensitivity in chronic heart failure.

BACKGROUND: Raised concentrations of endotoxin (lipopolysaccharides, LPS) have been demonstrated in patients with chronic heart failure (CHF). Tolerance of monocytes to LPS can be induced by negative feedback mechanism through LPS itself, resulting in a downregulation of cytokine response to LPS challenge. As endotoxin desensitization has also been suggested for CHF, we investigated the response to LPS challenge in CHF patients. METHODS: We prospectively studied 100 patients with CHF (62 +/- 13 years) and 21 controls (58 +/- 10 years, LVEF 60 +/- 3%). HLA-DR expression and TNFalpha generation of monocytes after ex vivo stimulation by LPS (stimulation with LPS 50 and 500 pg/ml) were determined. 46 CHF patients were in NYHA class II (LVEF 29 +/- 8%) and 54 in NYHA class III (LVEF 27 +/- 7%). RESULTS: HLA-DR expression in controls (25,837 +/- 7915 ABS/cell) was comparable to CHF NYHA II patients (23,720 +/- 8488 ABS/cell, n.s.), but lower in patients classified NYHA III (20,327 +/- 5073 ABS/cell, p < 0.01). Stimulated TNFalpha production ex vivo was higher in CHF NYHA III (LPS 50: 437 +/- 284; LPS 500: 946 +/- 500 pg/ml, each p < 0.05) and CHF NYHA II (LPS 50: 397 +/- 277; LPS 500: 933 +/- 483 pg/ml, each p < 0.05) compared to controls (LPS 50: 315 +/- 134; LPS 500: 715 +/- 339 pg/ml). CONCLUSIONS: In chronic heart failure TNFalpha generation capacity increases while HLA-DR expression decreases compared to controls. Thus patients with CHF display enhanced susceptibility to inflammatory stimuli.

Aged↗
PubMed2006

[Required monitoring in the intensive care unit].

Monitoring of the critically ill patient with acute heart failure still remains a special challenge for intensive care physicians. A rapid change of the patients' condition is subject to the underlying disease and even cardiac arrest may occur without preliminary warnings. The continuous monitoring of heart rate and rhythm, as well as noninvasive measurement of blood pressure, body temperature and urine elimination are obligatory components of the so-called standard monitoring. In addition, the modular concepts of the present-day monitoring systems become endorsed by techniques such as twelve-lead electrocardiogram and the obligatory echocardiography. Moreover, determination of biochemical markers depends on the clinical problem. The indications for invasive cardiovascular hemodynamic monitoring with pulmonary artery catheter or with less invasive techniques--such as pulse contour analysis or thermal dye dilution technique--must be placed critically. There is no evidence at all that prognosis is changed by implementation of a monitoring technique.

Critical Care↗
PubMed2006

The value of cardiopulmonary exercise testing and brain natriuretic peptide plasma levels in predicting the prognosis of patients with chronic heart failure.

BACKGROUND: A peak VO2 above 14 ml/min/kg at cardiopulmonary exercise testing and brain natriuretic peptide (BNP) levels is used to estimate survival in patients with chronic heart failure (CHF). Limited data, however, exist comparing the prognostic value of both markers simultaneously in patients with mild to moderate CHF. METHODS: We prospectively studied 85 consecutive patients (59+/-13 years, 63 men) with CHF (mean LVEF 26+/-6%). All patients underwent cardiopulmonary exercise testing with determination of peak VO2 and measurement of plasma BNP at rest. The incidence of cardiac decompensation and cardiac death was recorded in the follow-up. RESULTS: During a mean follow-up of 427+/-150 days, four deaths and ten cardiac decompensations occurred. Kaplan-Meier estimates of freedom from clinical events differed significantly for patients above and below the median BNP of 292 pg/ml and also for patients above and below a peak VO2 of 14 ml/min/kg (p<0.05 each). BNP and peak VO2 (area under the ROC 0.75 vs. 0.72) showed a comparable discrimination of CHF patients with adverse cardiac events. The prognostic information of BNP was at least as powerful as that derived from peak VO2. A BNP above 324 pg/ml was associated with a risk ratio of 8.8 for adverse cardiac events. CONCLUSIONS: In patients with mild to moderate CHF, BNP measurements appear to be an alternative to peak VO2 determined by cardiopulmonary exercise testing for the assessment of prognosis in CHF. BNP may facilitate the ambulatory management of patients with mild to moderate CHF since it is less expensive, less time-consuming, and free of procedural risk compared to exercise testing.

Journal Article↗
PubMed2006

The prognostic value of early transcranial Doppler ultrasound following cardiopulmonary resuscitation.

The aim of the presented study was to estimate the prognostic value of transcranial Doppler sonography (TCD) for the prediction of clinical outcome of patients after cardiopulmonary resuscitation (CPR) on the basis of the measured flow velocity changes in the basal cerebral arteries. Thirty-nine patients (27 men, 12 women) aged 66 +/- 15 y (+/-SD) who had undergone CPR were involved. Serial TCD examinations of the intracranial arteries were performed 1.5, 4, 8, 16, 24 and 72 h after CPR. Plasma neuron specific enolase (NSE), ventilation parameters (pH, paO(2), paCO(2)) and hemodynamic parameters were registered. Seventeen patients (group 1) survived with moderate or without neurologic deficits. Twenty-two patients (group 2) either died (n = 21) within 9 +/- 14 days or remained in vegetative state (n = 1). NSE levels ranged from 9 to 29 microg/L in group 1 and from 22 to 1242 microg/L in group 2 (p < 0.05). Four and 72 h after CPR, peak systolic flow velocities in the middle cerebral artery (MCA) were significantly higher in group 1 than in group 2 (p < 0.05). Twenty-four h after CPR, peak systolic and diastolic flow velocities in the ACA and PCA were also significantly higher in group 1 than in group 2 (p < 0.05). At this time, patients of group 2 showed significantly higher resistance index-values (RI = (sys-dia)/sys) in the anterior cerebral artery (ACA) and the posterior cerebral artery (PCA) (p < 0.05). A high correlation between peak systolic blood flow velocity in the MCA and systemic systolic blood pressure was observed in group 2 early 4 to 16 h after CPR (r = +0.52 to + 0.81, p < 0.05), while there was no such correlation in group 1. Using serial TCD examinations, patients with severely disabling or fatal outcome could be identified within the first 24 h. Besides established clinical and laboratory parameters, postanoxic myoclonus and NSE, serial TCD examinations following CPR may be helpful to predict the clinical outcome, but further studies with a larger number of patients are necessary to approve this hypothesis.

Adolescent↗
PubMed2005

Additive effects of the chemokine receptor 2, vitamin D receptor, interleukin-6 polymorphisms and cardiovascular risk factors on the prevalence of myocardial infarction in patients below 65 years.

BACKGROUND: Cardiovascular risk factors (CRF) have been associated with myocardial infarction (MI), while the role of genetic risk factors (GRF) remains undetermined. METHODS: Cineventriculograms of 3436 were analyzed for presence of regional function impairment as sign of MI. Genotyping for genetic polymorphism (vitamin D receptor VDR BsmI, interleukin-6 IL6-174 G/C, chemokine receptor 2 CCR2 64 V/I) was performed. CRF were assessed (hypertension, hypercholesterolemia, smoking, and diabetes mellitus). RESULTS: In patients <65 years (n=1946) genotypes (VDR BB, IL6 GC/CC, CCR2 VI/II, defined as GRF) were significantly associated with the presence of MI (BB: OR 1.38, 95%CI 1.07-1.79, p=0.016 GC/CC: 1.28, 95%CI 1.03-1.60, p=0.028 VI/II: 1.49, 95%CI 1.17-1.88, p=0.001). Combining four CRF (14% vs. 21% vs. 27% vs. 31% vs. 38%, p<0.0001) and three GRF (21% vs. 25% vs. 32% vs. 44%, p<0.0001) revealed additive effects on the prevalence of MI. The more combined CRF and GRF were present (from 0 to 7) the higher was the prevalence of MI (11% vs. 12% vs. 21% vs. 27% vs. 30% vs. 34% vs. 59%, p< 0.0001). Age was not associated with MI. In patients > or =65 years (n=1490) the combination of CRF was only weakly associated with MI, while GRF were not. In these patients age was a predictor of MI. CONCLUSION: Certain GRF might have additive but small effects on the disposition for MI before the age of 65. In older patients the tested GRF had no effect, possibly indicating a mechanism of aging rather than a purely genetic determined entity. Given the small effect of the tested genetic polymorphisms the value of testing GRF remains uncertain.

Age Factors↗
PubMed2005

Noninvasive home telemonitoring for patients with heart failure at high risk of recurrent admission and death: the Trans-European Network-Home-Care Management System (TEN-HMS) study.

OBJECTIVES: We sought to identify whether home telemonitoring (HTM) improves outcomes compared with nurse telephone support (NTS) and usual care (UC) for patients with heart failure who are at high risk of hospitalization or death. BACKGROUND: Heart failure is associated with a high rate of hospitalization and poor prognosis. Telemonitoring could help implement and maintain effective therapy and detect worsening heart failure and its cause promptly to prevent medical crises. METHODS: Patients with a recent admission for heart failure and left ventricular ejection fraction (LVEF) <40% were assigned randomly to HTM, NTS, or UC in a 2:2:1 ratio. HTM consisted of twice-daily patient self-measurement of weight, blood pressure, heart rate, and rhythm with automated devices linked to a cardiology center. The NTS consisted of specialist nurses who were available to patients by telephone. Primary care physicians delivered UC. The primary end point was days dead or hospitalized with NTS versus HTM at 240 days. RESULTS: Of 426 patients randomly assigned, 48% were aged >70 years, mean LVEF was 25% (SD, 8) and median plasma N-terminal pro-brain natriuretic peptide was 3,070 pg/ml (interquartile range 1,285 to 6,749 pg/ml). During 240 days of follow-up, 19.5%, 15.9%, and 12.7% of days were lost as the result of death or hospitalization for UC, NTS, and HTM, respectively (no significant difference). The number of admissions and mortality were similar among patients randomly assigned to NTS or HTM, but the mean duration of admissions was reduced by 6 days (95% confidence interval 1 to 11) with HTM. Patients randomly assigned to receive UC had higher one-year mortality (45%) than patients assigned to receive NTS (27%) or HTM (29%) (p = 0.032). CONCLUSIONS: Further investigation and refinement of the application of HTM are warranted because it may be a valuable role for the management of selected patients with heart failure.

Aged↗
PubMed2005

Recommendations for the structure, organization, and operation of intensive cardiac care units.

Two major changes in patient characteristics and management occurred recently that demand distinctive alterations in the function of the intensive cardiac care unit (ICCU). These changes include the introduction of an early invasive strategy for the treatment of acute coronary syndromes, enabling early recuperation and shorter need for intensive care on the one hand, while the number of older and sicker patients requiring prolonged and more complex intensive care is steadily increasing. A task force of the European Society of Cardiology Working Group on Acute Cardiac Care was set to give a modern updated comprehensive recommendations concerning the structure, organization, and function of the modern ICCUs and intermediate cardiac units. These include the statement that specially trained cardiologists and cardiac nurses who can manage patients with acute cardiac conditions should staff the ICCUs. The optimum number of physicians, nurses, and other personal working in the unit is included. The document indicates the desired architecture and structure of the units and the intermediate cardiac unit and their relations to the other facilities in the hospital. Specific recommendations are also included for the minimal number of beds, monitoring system, respirators, pacemaker/defibrillators, and necessary additional equipment. The desired function is discussed, namely, the patients to be admitted, the length of stay, and the relocation policy. A uniformed electronic chart for ICCUs is advised, anticipating a common European database.

Coronary Care Units↗
PubMed2005

Relationship of five inflammatory gene polymorphisms with morbidity and mortality in 533 patients admitted to an ICU.

BACKGROUND: The aim of this study was to analyze the association of polymorphisms of five candidate genes with the outcome of consecutive patients admitted to a medical ICU. MATERIALS AND METHODS: The study population was prospectively recruited. Inclusion criteria were admission to the ICU and written informed consent by the patients or their relatives. A total of 533 patients were recruited. The morbidity was assessed by SAPS II Score. Outcome data of in hospital mortality and length of ICU and hospital stay were obtained. Genotyping for genetic polymorphisms (CRP 1059, IL1B -511, CTGF -477, CCR2 64VI, IL6 -174) were performed by allele-specific fluorogenic oligonucleotide probes (TaqMan analysis). RESULTS: All of the investigated polymorphisms were not associated with an altered outcome. There was no difference in morbidity and ICU or in-hospital mortality (neither in cross tabs analysis nor in Kaplan Meier or Cox regression analysis including age, gender and diagnosis as covariates) between the different genotypes. CONCLUSIONS: Genotyping of the investigated polymorphism for risk stratification of patients admitted to ICU does not seem to be appropriated.

Aged↗
PubMed2005

CD14 gene -260 C/T polymorphism is associated with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) show inflammatory changes and elevated plasma levels of TNFalpha and endotoxins. However, the role of the CD14 C(-260)T polymorphism in patients with CHF is unclear. Therefore, we sought to determine whether the C=>T promoter polymorphism (position -260) of the CD 14 gene is associated with a higher risk for the development of CHF. METHODS: We studied 100 patients with CHF (mean age 62+/-3 years, LVEF 28+/-8%) and 100 healthy controls (59+/-10 years, p=NS; LVEF 60+/-4%, p<0.05). CD14 genotyping was performed using a PCR-RFLP technique. RESULTS: Among CHF patients, the frequency of the T allele was lower (38% vs. 48%, p<0.05) and the frequency of the C allele higher (62 % vs. 52 %, p<0.05) than among controls. The distribution of CD14 genotypes in healthy controls was as follows: CC 32%, CT 40%, and TT 28%. Among CHF patients, the TT genotype was significantly underrepresented compared to controls: CC 38%, CT 48%, and TT 14% (p<0.05). CONCLUSIONS: The C -260T polymorphism of CD14 seems to influence the susceptibility for the development of CHF. The T allele is less frequent among CHF patients than among controls. The TT genotype could be a new genetic protective factor against the development of CHF.

Journal Article↗
PubMed2005

Urotensin II in patients with chronic heart failure.

BACKGROUND: Human Urotensin II (hU-II) is the most potent vasoconstrictor known to date. HU-II receptors are predominant in the human heart and arterial vessels, suggesting hU-II to be of importance as a cardiovascular mediator. METHODS: We studied 32 consecutive patients (60+/-12 years) with chronic heart failure (CHF) and 10 control subjects (54+/-12 years, n.s.) with cardiopulmonary exercise testing. Blood samples for the measurement of plasma hU-II and big-endothelin-1 (big-ET1) were obtained at rest and at peak exercise. RESULTS: Peak VO(2) was significantly higher in controls than in CHF patients (19.8+/-3.8 vs. 14.7+/-3.6 ml min(-1) kg(-1), P<0.001). Big-ET1 levels were increased in CHF compared to controls at rest (2.8+/-1.8 vs. 1.7+/-0.1 fmol/ml, P<0.01) and at peak exercise (2.7+/-1.7 vs. 1.6+/-0.2 fmol/ml, P<0.005). HU-II concentrations were comparable in patients with CHF and controls at rest (2990+/-1104 vs. 3290+/-508 pg/ml, n.s.) and peak exercise (3063+/-1185 vs. 3213+/-1188 pg/ml, n.s.). Resting hU-II levels demonstrated no correlation with peak VO(2) in controls or CHF patients. CONCLUSIONS: The measurement of circulating plasma levels of hU-II does not seem to be very helpful in studying the effects of hU-II in human cardiovascular regulation. A local paracrine or autocrine mediator effect of hU-II in CHF is possible.

Aged↗
PubMed2005

Five-year survival, quality of life, and individual costs of 303 consecutive medical intensive care patients--a cost-utility analysis.

OBJECTIVE: To assess long-term survival, health-related quality of life, and associated costs 5 yrs after discharge from a medical intensive care unit. DESIGN: Prospective cohort study. SETTING: Medical intensive care unit of a German university hospital. PATIENTS: Three hundred and three consecutive patients with predominantly cardiovascular and pulmonary disorders admitted between November 1997 and February 1998 with an intensive care unit length of stay >24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, simplified Therapeutic Intervention Scoring System, and individual intensive care unit and hospital costs were prospectively recorded. Primary outcomes included 5-yr survival, functional status, health-related quality of life (Medical Outcome Short Form, SF-36), effective costs per survivor, and costs per life year and per quality-adjusted life year gained. Of 303 patients, 44 (14.5%) died in the hospital. Among the remaining 259 patients, 190 (73%) survived the 5-yr follow up and 173 patients (91%) completed the questionnaire. Baseline demographics including gender, age, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment, simplified Therapeutic Intervention Scoring System, and admission diagnosis were similar between hospital and long-term survivors (p > .05 for all). The health status index of those patients surviving the 5-yr follow-up was 0.88, independent of patients' severity of illness. The average effective costs per survivor were 8.827 for intensive care unit costs and 14.130 for intensive care unit and hospital costs. Mean costs per life year and per quality-adjusted life year gained amounted to 19.330 and 21.922 , respectively. Increasing severity of illness was associated with higher costs. CONCLUSIONS: Considering the severity of illness and the patients' outcome, the costs associated with both life year and quality-adjusted life year gained were within generally accepted limits for other potentially life-saving treatments.

APACHE↗
PubMed2004

HMG-CoA reductase inhibitor simvastatin profoundly improves survival in a murine model of sepsis.

BACKGROUND: HMG-CoA reductase inhibitors, such as simvastatin, have been shown to exhibit pronounced immunomodulatory effects independent of lipid lowering but to date have not been used to treat severe inflammatory disease such as sepsis. We thus approached the question of whether treatment with simvastatin might improve cardiovascular function and survival in sepsis. METHODS AND RESULTS: Mice treated with simvastatin and rendered septic by cecal ligation and perforation (CLP) show a mean survival time close to 4 times the value found in untreated mice. This dramatic improvement is based on a complete preservation of cardiac function and hemodynamic status, which are severely impaired in untreated CLP mice [eg, 20 hours after CLP, cardiac output declined from 1.24+/-0.09 to 0.87+/-0.11 mL x min(-1) x g(-1) in untreated mice (P<0.005; n=12), while remaining unaltered (1.21+/-0.08 mL x min(-1) x g(-1) at baseline and 1.15+/-0.1 mL x min(-1) x g(-1) 20 hours after CLP, P=NS, n=12) in CLP mice treated with simvastatin]. Untreated CLP mice remained refractory to beta-stimulation, whereas the responsiveness to dobutamine was restored by treatment with simvastatin. Susceptibility of coronary flow to endothelial nitric oxide synthase (eNOS) stimulation by bradykinin was close to 3 times as pronounced in untreated CLP mice as in untreated sham-operated mice, indicating a high level of eNOS activation secondary to sepsis. In addition, treatment with simvastatin reversed inflammatory alterations in CLP mice, namely, increased monocyte adhesion to endothelium. CONCLUSIONS: Simvastatin, which is well established in the treatment of lipid disorders and coronary artery disease, might have the additional potential of being an effective agent in sepsis treatment.

Animals↗
PubMed2004

Endotoxin sensitivity and immune competence in chronic heart failure.

BACKGROUND: Raised concentrations of endotoxin (lipopolysaccharide, LPS) are found in patients with chronic heart failure (CHF). Tolerance of monocytes to LPS can be induced by LPS itself resulting in a downregulation of cytokine response to LPS challenge. This phenomenon of LPS desensitization has also been suggested for CHF. METHODS: We investigated whether CHF patients really show a desensitization to LPS stimuli at rest or after physical exercise, which was used as a model of limited inflammatory reaction. Thirty-five patients with CHF (59+/-12 years, 8 women) and 30 healthy control subjects were prospectively studied with cardiopulmonary exercise testing. At rest and directly after exercise blood samples were taken for the quantitative determination of HLA-DR expression of monocytes as a measure for immune competence and for the measurement of TNFalpha generation after ex vivo stimulation by LPS. RESULTS: HLA-DR expression was comparable in CHF patients and controls at rest as well as after exercise. TNFalpha production by LPS-stimulated monocytes ex vivo was higher in CHF patients compared to controls at rest and after exercise. CONCLUSIONS: Thus, our data are the first to show that patients with stable CHF show a cellular hypersensitivity to LPS with a higher TNFalpha generation capacity at rest and after exercise compared to controls. CHF patients seem to have a marked susceptibility to low inflammatory stimuli and no desensitization to LPS.

Female↗
PubMed2004

Relaxin kinetics during dynamic exercise in patients with chronic heart failure.

Background: We investigated circulating relaxin (RLX) and its potential role in human congestive heart failure (CHF) at rest and after physical exercise. Methods: A total of 10 healthy controls and 35 patients with stable CHF were enrolled in the study. Results: RLX plasma concentrations at rest and after exercise were comparable in patients with CHF and in controls. Conclusion: These findings suggest that RLX does not play a major role as a circulating hormone in human CHF.

Journal Article↗