Search PubMed⌕ Search

Biomedical subjects

W J Kox

Publications and source records attributed to W J Kox.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Candida antigen and antibody kinetics during antifungal therapy in non-neutropenic intensive care patients].

The present study aimed at determining Candida antigen and antibody kinetics during antifungal therapy. 115 non-neutropenic patients with a stay of more than 5 days in an interdisciplinary intensive care unit during a period of 2 years were reviewed. Routinely measured Candida antigen and antibody titers were evaluated at the beginning and during antifungal therapy. In 67 patients serological data were evaluable in defined time slots. Under fluconazole therapy (FT) the median of Candida antigen (Ramco) was 1:4 and did not change significantly. Candida antibody level increased from 1:80 to 1:320. Initial titers between FT and amphotericin B/5-fluorocytosine therapy (AT) showed a significant difference. During AT antigen titers decreased from 1:8 to 1:4 while antibody titers kept constant at a level of 1:160.

Amphotericin B↗
PubMed1999

Monocyte stimulation by reactive oxygen species: role of superoxide and intracellular Ca2+.

OBJECTIVE: Production of reactive oxygen species has generally been linked to inflammatory processes. Whether the presence of superoxide and hydrogen peroxide affects mononuclear cell function was investigated with an in vitro model using isolated human mononuclear cells. MATERIALS AND METHODS: Human mononuclear cells were isolated from buffy coat. Toxicity was measured with Trypan blue exclusion, secreted TNF-alpha was measured with an ELISA, reactive oxygen species within mononuclear cells were quantified with dichlorodihydrofluorescein diacetate fluorescence, intracellular TNF-alpha was measured with flow cytometry and fluorescence microscopy. RESULTS: The enzymatic production of superoxide caused a dose-dependent increase in TNF-alpha synthesis, whereas hydrogen peroxide was ineffective. Flow cytometric measurements and immunofluorescence microscopy demonstrated that monocytes were the main TNF-alpha producing population. This proinflammatory reaction was further characterized by pharmacologically investigating Ca2+ signalling pathways. Superoxide stimulated TNF-alpha secretion was inhibited by intracellular Ca2+-buffers (MAPT-AM and BAPT-AM) or VOC operating antagonists (diltiazem and verapamil) and only to a small extent by pharmacological inhibitors of ligand-gated pathways (TMB-8 and SKF 96368). CONCLUSION: We propose that superoxide activates human mononuclear cells in a Ca2+-dependent manner.

Calcium↗
PubMed1999

Bleeding after intermittent or continuous r-hirudin during CVVH.

OBJECTIVE: To demonstrate bleeding complications encountered in patients after cardiac surgery on continuous venovenous haemofiltration (CVVH) treated with continuous versus intermittent r-hirudin for heparin-induced thrombocytopenia (HIT) type II. DESIGN: Case description. SETTING: Cardiothoracic intensive care unit at a university hospital. PATIENTS: 5 consecutive patients with proven HIT type II on CVVH after major cardiac surgery. INTERVENTIONS: Recombinant hirudin (r-hirudin) was given continuously at a dose of 0.01 mg/kg per h in three patients or in repeated bolus administration of 0.05 mg/kg in two patients. MEASUREMENTS AND RESULTS: Since the ecarin clotting time assay was not available at that time to monitor hirudin effects on coagulation, the activated partial thromboplastin time (normal range 26-38 s, target range 50-60 s) was used. The continuously treated patients suffered from major bleeding complications. Therefore, the regimen was changed to repeated bolus administration, reducing the incidence of bleeding complications probably due to a threefold diminished cumulative hirudin dose per day in comparison to continuous administration. CONCLUSIONS: If ecarin clotting time, the most suitable monitor for hirudin activation, is not available, we would prefer to give r-hirudin in repeated boluses to avoid major bleeding complications in cardiac surgery patients on CVVH.

Aged↗
PubMed1999

Impact of standard procedures and clinical standards on cost-effectiveness and intensive care unit performance in adult patients after cardiac surgery.

OBJECTIVE: To investigate the impact of organizational procedures on intensive care unit (ICU) performance and cost-effectiveness after cardiac surgery. DESIGN: Prospective study. SETTING: Cardiothoracic ICU at a university hospital. PATIENTS: Thousand five hundred twenty-six consecutive patients over a period of 18 months. INTERVENTIONS: The first 6 months were used as the control period. Afterwards selected organizational changes were introduced, such as written standard procedures, time schedules and discharge reports. MEASUREMENTS: Demographic data, surgical procedures, length of ICU and hospital stay and hospital outcome were recorded. Severity of illness was assessed daily using Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS II) and Organ Failure Score (OFS). Intensity of treatment and nursing care was monitored by the Therapeutic Intervention Scoring System (TISS). RIYADH ICU Program (RIP 5.0) was used to determine the relationship of observed to predicted mortality (standardized mortality ratio SMR) and the effective costs per survivor. MAIN RESULTS: SMR decreased continuously after the establishment of new management procedures while all other factors all other factors remained unchanged. Comparing outcome according to APACHE II on ICU admission demonstrated a significantly increased ICU performance in high risk patients with an APACHE II of 20-30 points (p < 0.05) while effective costs per survivor decreased significantly from DM 29,988 to DM 13,568 DM (p < 0.05). CONCLUSIONS: Organizational changes can improve ICU performance and cost-effectiveness after cardiac surgery. The RIP may be used to monitor the clinical and economical effects of change.

APACHE↗
PubMed1999

Xenon-induced inhibition of Ca2+-regulated transitions in the cell cycle of human endothelial cells.

Xenon is an anesthetic with very few side-effects, yet its targets at the cellular level are still unclear. It interferes with many aspects of intracellular Ca2+ homeostasis, but so far no specific event or defined regulatory complex of the Ca2+-signaling system has been identified. Specific effects of xenon were found by investigating its effects on the cell cycle in human endothelial cells: there is a relationship between two cell cycle transition points, their regulation by Ca2+, and specific blocks induced by xenon. Within the group of substances studied (xenon, isoflurane, desflurane, helium, and N2), only xenon blocks the cells almost completely at the G2-M transition after a 2-h treatment; those cells that slip through this block are then arrested at metaphase. If xenon is removed, cells that have been accumulating at the G2-M boundary move into mitosis, and cells blocked at metaphase complete their mitosis normally. No such specific block of the cell cycle was found with the other substances studied. An artificial increase of intracellular Ca2+ in the submicromolar range, using a very low dose of the Ca2+ ionophore ionomycin, or a threefold increase of the external Ca2+ concentration suffices to lift the xenon-induced metaphase block; the cells enter anaphase despite the presence of xenon and complete cell division. Thus, the specific but completely reversible inhibition by xenon of the G2-M transition and the block at metaphase suggest an interaction with a Ca2+-dependent event involved in the control of these processes. The results are consistent with the hypothesis that suppression of Ca2+ signals can be considered as a common denominator of the effects of xenon on the cell cycle and on the neuronal system during anesthesia.

Anesthetics, Inhalation↗
PubMed1999

Xenon induces metaphase arrest in rat astrocytes.

The use of xenon as an almost ideal anesthetic with very little side effects is gaining clinical acceptance, yet its effects on the cellular level are still unclear. It affects intracellular Ca2+-homeostasis but up to now no cellular event or Ca2+-signaling system has been described to be specifically sensitive to xenon. Here we report for the first time a specific effect of xenon on astroglial cells not found with another volatile anesthetic, isoflurane, nor with helium nor with N2: treatment of primary astroglial cells from embryonic rat brain with xenon induces, apart from a slight retardation of the cell cycle, a block at metaphase. Upon removal of xenon cells arrested at metaphase complete their mitosis normally. Even under continuous exposure to xenon, cells can be rescued from metaphase arrest by a small and transient increase in intracellular Ca2+; cells enter anaphase despite the presence of xenon and complete cell division, exhibiting normal rate of chromosome movement and normal chromosome separation. These results suggest that xenon interferes with some Ca2+-dependent regulatory system required for the metaphase-anaphase transition; taking into account its anesthetic effects, xenon may be also involved in the control of glia-mediated signaling transfer.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

Reduction of cell density dependent antigenic properties of intracellular Ca(2+)-regulating membranes by isoflurane in human endothelial cells.

An established cell line of human umbilical vein endothelial cells displays a pronounced shift in the distribution of intracellular Ca(2+)-regulating membranes as the cells grow towards confluence. In sparsely populated cultures a linearly oriented punctate pattern of vesicle-like structures is observed similar to the distribution found in many other eucaryotic cells. As the cell population increases, the membranes condense around the nucleus. In completely confluent cultures when the cells cease to proliferate, the antigen is no longer detectable by immunofluorescence; its absence is confirmed by Western blotting experiments. Double-labeling with antitubulin or phalloidin shows that the distribution of microtubules is not related to the distribution of the Ca(2+)-regulating membranes whereas the actin fibers are superimposable onto the linearly oriented punctate vesicle-like structures. If proliferating cells are treated with the volatile anesthetic isoflurane, the Ca(2+)-regulating membranes can no longer be detected with the antibody; however, in Western blots the antigen is still present. Staining is restored after the removal of isoflurane. Such a temporary disappearance of the immunocytochemical staining might be explained by a transient oxidation and subsequent configuration change of the antigen, rendering the epitope inaccessible to the antibody, since a treatment with low concentrations of NaBH4 of cells exposed to isoflurane restores the access of the antigen to the antibody.

Anesthetics, Inhalation↗
PubMed1999

Oxidized proteins as a marker of oxidative stress during coronary heart surgery.

The measurement of the degree of oxidative stress in patients often causes problems because of the lack of useful parameters. Therefore, we used an ELISA technique to evaluate serum protein carbonyls as a parameter of oxidative stress in patients during coronary heart surgery. Protein carbonyls were detected in serum samples of 14 patients undergoing coronary surgery and cardiopulmonary artery bypass grafting. A clear 2- to 3-fold increase in protein carbonyls in serum samples taken from human venous coronary sinus could be detected in the reperfusion period of the heart. We compared these data with markers of oxidative stress previously used, such as the glutathione status and the lipid peroxidation product malondialdehyde (MDA). Strong correlations of the protein carbonyl formation with MDA (r2 = 0.86) and oxidized glutathione (r2 = 0.81) were found in the early reperfusion stage. Increased levels of oxidized glutathione and MDA were detected only in the early reperfusion period. In contrast, the serum protein carbonyl content remained elevated for several hours, indicating a considerably slower serum clearance of oxidized proteins compared with that of lipid peroxidation products and the normalization of the glutathione status. We therefore concluded that the measurement of serum carbonyls by this ELISA technique is suitable to detect oxidative stress in serum samples of patients. The relative stability of the parameter makes the protein carbonyl detection even more valuable for clinical purposes.

Aged↗
PubMed1999

[Forced opioid detoxification under general anesthesia--a new challenge for anesthetists and intensive care physicians].

Treatment of opioid addicts by means of competitive opioid receptor antagonists was developed at the University of Vienna in 1987 by Loimer and co-workers. They compared two withdrawal regimens: The short Opiate withdrawal using a staggered naloxone regimen and the rapid opiate detoxification during general anesthesia by means of high doses of naloxone. Based on the latter concept, various modifications have been developed world-wide using either naloxone or as an alternative, naltrexone, an antagonist available for oral administration only. However, there are considerable objections to opioid detoxification during general anasthesia. The main criticism is based an the supposedly unacceptable high risk:benefit-ratio, the higher costs, the lack of psycho-social support, and the lack of prospective studies. However, first results suggest that rapid detoxification procedures are more successful in decreasing relapse than methods which are based on psychiatric treatment alone. As sympathetic hyperfunction is common in rapid detoxification procedures using high doses of opioid receptor antagonists, it is essential to avoid severe autonomic imbalance with possible subsequent impairment of organ functions. To prevent those disturbances, general anesthesia plays an important role. So far, there is almost no information about such methods in the anesthesiological literature. In this article the clinical relevance of such methods is discussed summarizing both the available literature and our own experience and we conclude that rapid opioid detoxification under general anesthesia is a safe and efficient method to suppress withdrawal symptoms. This treatment may be of benefit in patients who particularly suffer from severe withdrawal symptoms and who have failed repeatedly to complete conventional withdrawal.

Anesthesia, General↗
PubMed1999

Inhibition of tumor necrosis factor-alpha release in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G.

OBJECTIVE: To determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-alpha release in experimental endotoxemia. DESIGN: Prospective, randomized, controlled animal study. SETTING: Experimental laboratory. SUBJECTS: Twenty-one male Wistar rats weighing 190+/-40 g. INTERVENTIONS: The rats were divided equally into 3 groups: a) control; b) endotoxemia (5 mg/kg lipopolysaccharide [LPS] from Escherichia coli 055:B5); and c) endotoxemia and U-74389G administration 30 mins before (3 mg/kg) and 60 mins after (1.5 mg/kg) endotoxin challenge. MEASUREMENTS AND MAIN RESULTS: At 0, 120, and 240 mins, serum levels of TNF-alpha were measured using a specific rat TNF-alpha ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-alpha release 120 mins after endotoxin challenge (control, 2.5+/-2.1 pg/mL; LPS, 4041+/-871 pg/mL; U-74389G, 1627+/-474 pg/mL [p < .05]). Two hundred forty minutes after LPS administration, TNF-alpha levels decreased, whereas values in the untreated LPS group remained twice as high as those in the U-74389G group (LPS, 863+/-182 pg/mL; U-74389G, 369+/-54 pg/mL [p < .05]). CONCLUSIONS: The study demonstrated that administration of U-74389G, which has radical-scavenging and membrane-stabilizing properties, decreased TNF-alpha release during endotoxemia. Thus, 21-aminosteroids may lend themselves to evaluation in the treatment of septic states.

Analysis of Variance↗
PubMed1999

Increased intrapulmonary oxygen consumption in mechanically ventilated patients with pneumonia.

Pulmonary oxygen consumption (V(O2)pulm) is believed to be increased in patients with lung infection. In the present study, VO2pulm was estimated from the difference between total oxygen consumption measured with indirect calorimetry (V(O2)cal) and oxygen consumption assessed with the reverse Fick method (V(O2)Fick). Seventy-five patients requiring mechanical ventilation were included, and were divided for analysis into two groups according to the existence (n = 41) or absence (n = 34) of pneumonia. V(O2)pulm was correlated with various parameters of impaired lung function. To assess the metabolic function of the lung, the differences in lactate and glucose concentrations at different arterial-mixed venous concentrations were determined and transpulmonary lactate flux as well as glucose flux was calculated. As compared with V(O2)pulm in patients without pneumonia (19.4 +/- 1.2 ml/ min/m2), V(O2)pulm was significantly increased in patients with pneumonia (50.7 +/- 1.7 ml/min/m2 (p < 0.001). For intrapatient measurements of V(O2)pulm, a sufficient reproducibility was achieved. V(O2)pulm increased with the lung injury score, number of afflicted lobes, venous admixture, the transpulmonary lactate flux, and the transpulmonary glucose flux, respectively. We speculate that the increased V(O2)pulm of infected lungs is due to different mechanisms, including increased oxidative metabolism by essentially extrapulmonary structures such as neutrophils and macrophages, as well as by changes in the metabolic function of lung tissue itself.

Blood Glucose↗
PubMed1998

Stimulation of monocytes and platelets by short-chain phosphatidylcholines with and without terminal carboxyl group.

Oxidation of unsaturated phosphatidylcholine (PC) produces fragmented phospholipids which have similar bioactivities as the platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-PC). Since a large number of molecular species are produced upon PC oxidation, the active ingredients have not been identified. We synthesized several short-chain PCs which are known to be characteristic PC oxidation products to test their PAF-like activity. The synthetic PCs contained palmitoyl or hexadecyl residues (both C16) in sn-1 position, and propionyl (C3), valeroyl (C5), succinyl (C4 with omega-carboxyl), glutaroyl (C5 with omega-carboxyl), or suberoyl (C8 with omega-carboxyl) residues in sn-2 position. Biological activity was measured by: (1) increase of intracellular calcium in human monocytes; (2) [3H]serotonin release from rabbit platelets; and (3) aggregation of human platelets. Specificity of the cellular response was tested by inhibition with the PAF-receptor antagonists BN 52021 and WEB 2086. Synthetic PC oxidation products activated both monocytes and platelets in a PAF-specific manner. The effective concentration varied with respect to assay system and chemical structure. In general, 1-hexadecyl-PCs were more effective than 1-palmitoyl-PCs, while increasing chain length in sn-2 position lowered biological activity. However, several 1-palmitoyl-PCs activated monocytes in concentrations between 10-8 and 10-6 M. In contrast, platelets were less susceptible to 1-palmitoyl-PCs. No significant difference was found between 2-valeroyl-PC (C5 with omega-methyl) and 2-glutaroyl-PC (C5 with omega-carboxyl). The data suggest that typical products of PC oxidation, containing propionyl, succinyl, or glutaroyl residues in sn-2 position, display PAF-like activity at micromolar concentrations.

Animals↗
PubMed1998

[FRC measurement in intensive care patients. A definition of standards].

Determination of Functional Residual Capacity (FRC) can be performed through washout methods, indicator gas dilution or bodyplethysmography. Some of these techniques have been adapted for use in intensive care patients whilst being mechanically ventilated. However, most measurement setups are bulky, cumbersome to use and their running costs are high. Hence FRC measurement has not become a routine method in intensive care although it offers considerable advantages in the management of ventilated patients such as the determination of "best PEEP", the detection of progressive alveolar collapse in the course of acute lung injury and during weaning from mechanical ventilation. Up to now most efforts to improve and simplify FRC measurement were made at the expense of accuracy. An ideal method ought to be accurate, easy to handle and cost-effective. It should supply not only FRC data but also information about intrapulmonary gas distribution and dead space. These demands can be met using modern data acquisition software. The pros and cons of all methods available for FRC measurement are discussed in view of their suitability for intensive care patients. A conventional nitrogen washout using emission spectroscopy for measurement of nitrogen concentration gives satisfying exact values for the determination of the parameters mentioned above. The measurement error can be lowered under 5% by special corrections for flow and nitrogen signal (delay and rise times, changes of gas viscosity). For flow measurement a normal pneumotachograph can be used. Using a laptop computer for data acquisition the bed-side monitor fulfills most of the demands in intensive care. It is then also possible to measure indices of intrapulmonary gas distribution such as Alveolar Mixing Efficiency and Lung Clearance Index.

Algorithms↗
PubMed1998

Increased microvascular water permeability in patients with septic shock, assessed with venous congestion plethysmography (VCP).

OBJECTIVES: To investigate microvascular water permeability (filtration capacity, Kf) in patients with septic and non-septic shock using a new non-invasive method for studying microvascular parameters in man. SETTING: Intensive Care Unit of a university hospital. PATIENTS AND METHODS: We investigated 28 patients, presenting with cardio-vascular instability due to either septic shock, or non-septic shock (haemorrhage, multiple trauma, respiratory and/or cardiac failure). INTERVENTIONS: We used standard invasive methods of monitoring (in-dwelling arterial lines and pulmonary artery flotation catheters) in combination with computer assisted venous congestion plethysmography (VCP) measurements, for a parallel assessment of peripheral microcirculatory parameters. RESULTS: On admission to the ICU, patients with septic shock revealed a significantly higher mean value of filtration capacity Kf = 6.1 +/- 0.4 x 10(-3) (mean value +/- standard error of the mean, ml.min-1.100 ml tissue-1.mmHg-1 = KfU) than non-septic patients Kf = 3.5 +/- 0.3 KfU (p < 0.02). The Kf values of the septic patients were significantly higher than those from age-matched patients with peripheral vascular disease (4.1 +/- 0.2 KfU, p < 0.001) and those of healthy controls (4.3 +/- 0.2 KfU, p < 0.001); the Kf values of the non-septic patients, however, were not significantly different. The highest mean Kf value observed during the stay on ICU was Kfmax 11.6 +/- 0.2 KfU in the septic group and 5.7 +/- 0.1 KfU in the non-septic group (p < 0.001). Pvi, a value reflecting the balance of hydrostatic and oncotic forces in the microcirculation, was elevated in both patient groups. On admission, in septic patients Pvi was 39.2 +/- 3.3 mmHg and in non-septic patients 35.1 +/- 2.7 mmHg, these values were not significantly different, but significantly higher than the Pvi value of healthy controls (Pvi 21.5 +/- 0.8) (p < 0.001). A weak, however significant, positive correlation was found between Kf and Pvi in both patient groups. No correlations were found between Kf, as well as Pvi, and cardiac index (CI), oxygen delivery index (DO2I), oxygen consumption index (VO2I) and systemic vascular resistance index (SVRI). CONCLUSIONS: An increase in permeability of microvessels will cause a loss of intravascular fluid and may therefore partially explain the large fluid requirements of patients in shock. It will also favour the development of oedema, which is often found in septic patients. We propose that changes in Kf are useful indices of microvascular malfunction and that VCP allows the non-invasive assessment of these parameters.

Adult↗
PubMed1998

Hyperleptinaemia in chronic heart failure. Relationships with insulin.

BACKGROUND: Leptin, a product of the ob gene, is known to increase energy expenditure. Given that chronic heart failure is a hypercatabolic state, we sought to determine whether congestive heart failure involves elevations in plasma leptin levels. Since leptin secretion is up-regulated by insulin, we also explored whether in congestive heart failure, a hyperinsulinaemic state, plasma leptin levels relate to plasma insulin levels. METHODS: Male patients with weight-stable congestive heart failure (n = 25, aged 55.5 +/- 2.0, mean +/- SEM, body mass index = 27.4 +/- 0.8, radionuclide left ventricular ejection fraction = 29.3 +/- 3.0%) and 18 controls, matched for age, sex and body fat (dual energy X-ray absorptiometry), underwent measurement of fasting plasma leptin (radioimmunoassay) and insulin levels. RESULTS: Compared to controls, patients with congestive heart failure had higher plasma leptin [8.12 (-1.12, +1.31) vs 4.48 (-0.61, +0.70) ng.ml-1, mean +/- asymmetrical SEM, P = 0.003], 41.5% higher plasma leptin per percent body fat mass (P < 0.001), and higher fasting insulin levels [67.8 (-11.1, +13.3) vs 32.9 (-5.7, +6.9) pmol.l-1, P = 0.010]. In the congestive heart failure group, plasma leptin correlated with total body fat (r = 0.66) and fasting insulin (r = 0.68) (both P < 0.001). In multivariate regression analyses of the congestive heart failure group, fasting insulin (standardized coefficient = 0.41, P = 0.011) emerged as a predictor of plasma leptin levels, independent of total body fat (standardized coefficient = 0.73, P = 0.002, R2 = 0.66, P < 0.001). CONCLUSIONS: Plasma leptin levels are raised in patients with congestive heart failure. The observation of a positive relationship between plasma leptin and insulin concentrations suggests that the insulin-leptin axis may be related to the increased energy expenditure observed in patients with congestive heart failure.

Adipose Tissue↗
PubMed1998

Uric acid in chronic heart failure: a marker of chronic inflammation.

BACKGROUND: Chronic heart failure is associated with hyperuricaemia and elevations in circulating markers of inflammation. Activation of xanthine oxidase, through free radical release, causes leukocyte and endothelial cell activation. Associations could therefore be expected between serum uric acid level, as a marker of increased xanthine oxidase activity, and markers of inflammation. We have explored these associations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic therapy and insulin resistance. METHODS AND RESULTS: Circulating uric acid and markers of inflammation were measured in 39 male patients with chronic heart failure and 16 healthy controls. All patients underwent a metabolic assessment, which provided a measure of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart failure had significantly higher levels of circulating uric acid, interleukin-6, soluble tumour necrosis factor receptor (sTNFR)-1, soluble intercellular adhesion molecule-1 (ICAM-1, all P<0.001), E-selectin and sTNFR2 (both P<0.05). In patients with chronic heart failure, serum uric acid concentrations correlated with circulating levels of sTNFR1 (r=0.74), interleukin-6 (r=0.66), sTNFR2 (r=0.63), TNFa (r=0.60) (all P<0.001), and ICAM-1 (r=0.41, P<0.01). In stepwise regression analyses, serum uric acid emerged as the strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol intake, serum creatinine, plasma insulin and glucose, and insulin sensitivity. CONCLUSIONS: Serum uric acid is strongly related to circulating markers of inflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory response in patients with chronic heart failure.

Cardiomyopathy, Dilated↗
PubMed1998

Tumour necrosis factor alpha as a predictor of impaired peak leg blood flow in patients with chronic heart failure.

Tumour necrosis factor alpha (TNF alpha) is increased in patients with cardiac cachexia, a condition associated with reduced peripheral blood flow both at rest and after interventions causing vasodilation. By contrast, in patients with chronic heart failure (CHF), higher TNF levels are associated with a greater capacity for vasodilation in the arm. To clarify the relationship between peripheral blood flow and TNF in CHF, we studied the relation between TNF alpha and blood flow in the leg (plethysmography, post maximal exercise and 5 min ischaemia) in 34 patients (age 63 +/- 2 years, ejection fraction 29 +/- 3%, peak VO2 16.6 +/- 1.1 ml/kg/min, mean +/- SEM). Peak leg blood flow correlated significantly with total TNF alpha (r = 0.68, p < 0.0001, peak VO2 (r = 0.54), and soluble TNF receptors 1 (r = 0.56) and 2 (r = 0.52, all p < 0.002). TNF alpha, soluble TNF receptors 1 and 2 and aldosterone correlated with peak blood flow independently of age, ejection fraction, peak VO2 and functional NYHA class. TNF alpha was the only parameter that showed strong correlations for peak blood flow in all clinically relevant subgroups (severe vs. mild, ischaemic vs. dilated, cachectic vs. non-cachectic patients). This study shows a close and inverse relationship between peak leg blood flow and the plasma concentration of TNF alpha, suggesting a pathophysiological role for TNF alpha in reducing peak peripheral blood flow in CHF.

Adult↗