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Biomedical subjects

L G Thijs

Publications and source records attributed to L G Thijs.

At least 19 recordsLinked to original sources
PubMed1995

Plasma levels of the chemokines monocyte chemotactic proteins-1 and -2 are elevated in human sepsis.

Because of their effects on monocytes, monocyte chemotactic proteins-1 and -2 (MCP-1 and MCP-2) may participate in the pathophysiology of sepsis. We measured circulating MCP-1 and MCP-2 levels in 42 septic patients having positive local or blood cultures. MCP-1 and MCP-2 levels were elevated in 24 (57%) and 25 (59%) of 42 septic patients, respectively, compared with healthy volunteers. Both patients with gram-positive and gram-negative infections had elevated MCP-1 plasma levels (P = .0001) and P < .0001), respectively; Mann-Whitney-U test), whereas patients with gram-positive infection, but not those with gram-negative infection, had increased MCP-2 plasma levels (P= .0182). No relative differences in MCP-1 and MCP-2 plasma levels were observed between several subgroups of patients (sepsis v septic shock; survivors v nonsurvivors), although levels of MCP-1 were the highest in patients with the more severe forms of sepsis, ie, those with shock or a lethal outcome. Serial observations showed that MCP-1 and MCP-2 plasma levels remained elevated for at least 48 hours. MCP-1 correlated weakly with interleukin-8 and MCP-2, the correlations for which were most pronounced in patients with septic shock. MCP-2 correlated with interleukin-8, and surprisingly, with the complement activation product C3a; these correlations further improved when analyzing patients with septic shock or when applying gram-positive infections. Thus, our results not only show increased MCP-1 and MCP-2 levels in patients with sepsis, but also suggest that the synthesis and release of MCP-1 and MCP-2 in sepsis are differently regulated in part.

Chemokine CCL2↗
PubMed1995

Disseminated aspergillosis after near-drowning.

We report a case of invasive pulmonary aspergillosis after near-drowning complicated by systemic disseminated disease to the heart, kidneys, left adrenal gland and brain. Detection of fungal micro-organisms in the sputum of near-drowning patients should be taken seriously.

Aspergillosis↗
PubMed1995

Abdominal compressions increase vital organ perfusion during CPR in dogs: relation with efficacy of thoracic compressions.

STUDY OBJECTIVE: Abdominal compressions can be interposed between the thoracic compressions of standard CPR (SCPR). The resulting interposed abdominal compression CPR (IAC-CPR) may increase blood pressures and patient survival, particularly if applied as a primary technique after in-hospital cardiac arrest. We used a predominant cardiac compression canine model to study the effects of IAC-CPR on blood pressures and total and vital organ perfusion as a function of time after cardiac arrest and efficacy of SCPR. DESIGN: In a crossover design, we measured blood pressures and total and regional blood flow (radioactive microspheres) during 6-minute episodes of mechanical SCPR and IAC-CPR, both early (4 to 16 minutes) and late (18 to 30 minutes) after induction of ventricular fibrillation in eight dogs (weight, 25 to 33 kg) under neuroleptanalgesia/anesthesia. RESULTS: During IAC-CPR, the ascending aortic-right atrial pressure gradient increased (P < .05), and retrograde pressure pulses contributed to the rise of ascending aortic pressure. Within 2 minutes after the start of IAC-CPR, end-tidal CO2 fraction increased by 0.6 +/- 0.4 vol% (P < .05), suggesting enhanced venous return. IAC-CPR enhanced (P < .05) total forward blood flow (574 +/- 406 versus 394 +/- 266 mL/minute during SCPR for the early phase) and vital organ perfusion (including myocardium), in both early and late phases. The IAC-CPR-induced augmentation of blood flow was greater if perfusion was relatively high during SCPR. CONCLUSION: Compared with predominant cardiac compressions alone (SCPR), the addition of interposed abdominal compressions (IAC-CPR) improves total and vital organ oxygen delivery through enhanced venous return and perfusion pressures.

Abdomen↗
PubMed1995

Effects of human growth hormone in critically ill nonseptic patients: results from a prospective, randomized, placebo-controlled trial.

OBJECTIVES: To study the effects of growth hormone administration on insulin-like growth factor I concentration, nitrogen balance, and fuel utilization, and to study its safety in critically ill nonseptic patients. DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Eighteen critically ill nonseptic patients were studied for 8 days after admission. INTERVENTIONS: Growth hormone (0.1 mg/kg/day) or placebo was administered as a continuous intravenous infusion on the second, third, and fourth days after admission. The study period was 8 days. MEASUREMENTS AND MAIN RESULTS: Plasma hormone concentrations were measured every 6 hrs and average daily values were calculated. The 24-hr urinary nitrogen and 3-methylhistidine excretion were measured. Indirect calorimetry was used to calculate fuel utilization. Insulin-like growth factor I concentrations increased in the treatment group from subnormal to normal values and remained increased despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance differed between the groups upon admission: growth hormone group (3.9 +/- 4.1 g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This finding appeared independent of the imbalance between the groups. The 3-methylhistidine excretion was not different between the groups and did not change during growth hormone administration. Free fatty acids and glycerol concentrations increased during growth hormone treatment, but calculated fuel utilization did not change. During growth hormone treatment, insulin concentrations increased, due to the increased administration of insulin necessary for glycemic control. Side effects other than hyperglycemia were not observed. CONCLUSIONS: Growth hormone administration in a heterogeneous group of critically ill nonseptic patients resulted in normalization of insulin-like growth factor I levels, even after cessation of growth hormone treatment. Nitrogen balance improved, but this change was transient. Hence, growth hormone affects nitrogen balance, probably partly independent of insulin-like growth factor I.

Blood Glucose↗
PubMed1995

Methylene blue increases myocardial function in septic shock.

OBJECTIVE: To study whether the circulatory changes of human septic shock are mediated in part by nitric oxide. DESIGN: Open-label, nonrandomized clinical trial on the effects of methylene blue, an inhibitor of nitric oxide action. SETTING: Intensive care unit of a teaching hospital. PATIENTS: Nine consecutive patients with documented septic shock and a pulmonary artery catheter in place, after initial resuscitation with fluids, sympathomimetics, and mechanical ventilation. INTERVENTIONS: Hemodynamic and metabolic variables were measured before and then 15, 30, 60, and 120 mins after the start of a 20-min infusion of 2 mg/kg of methylene blue. MEASUREMENTS AND MAIN RESULTS: Patients had a hyperdynamic circulation, and methylene blue increased (p < .01) mean arterial pressure from 84 +/- 18 to 109 +/- 31 mm Hg and cardiac index from 4.7 +/- 0.9 to 5.6 +/- 1.2 L/min/m2, before and 30 mins after starting the methylene blue infusion, respectively. Cardiac filling pressures did not change. In the same time interval, the subnormal systemic vascular resistance index increased (p = .09) and arterial compliance decreased (p < .05). Oxygen delivery and oxygen uptake increased (p < .05) from 714 +/- 188 to 865 +/- 250 mL/min/m2 and from 160 +/- 39 to 186 +/- 44 mL/min/m2, respectively. Except for heart rate, which increased by 11 +/- 8 beats/min (p < .01), variables returned to baseline values at time = 120 mins. CONCLUSIONS: After initial resuscitation from human septic shock, a single dose of methylene blue transiently increases mean arterial pressure and oxygen uptake, associated with a decrease in arterial compliance and increases in myocardial function and oxygen delivery. Hence, nitric oxide may be a mediator of the circulatory changes of human septic shock.

Aged↗
PubMed1995

Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Local mitochondrial enzyme activity correlates with myocardial blood flow at basal workloads.

To study whether heterogeneous myocardial blood flow relates to the local oxidative capacity of cardiac muscle, local blood flow at resting cardiac workloads and the activity of the mitochondrial enzyme succinate dehydrogenase (SDH) were determined in small regions of the left ventricle of seven anaesthetized, mechanically ventilated, open-chest pigs (25-35 kg). Following injection of radioactive microspheres (15 microns phi) into the left atrium, the heart was rapidly excised and cut into five transverse slices, which were simultaneously freeze-clamped between two aluminum blocks precooled at -80 degrees C. The left ventricle was then subdivided into 84 samples of about 0.9 g. Myocardial blood flow was 0.88 +/- 0.34 ml/min/g wet weight (ww), and SDH activity 1.46 +/- 0.33 mumol/min/g ww (mean +/- S.D., n = 7). Local data were normalized to their respective mean values in each pig, and then pooled. Local blood flow ranged from 0.32 to 1.63 of the mean, and blood flow heterogeneity characterized by the coefficient of variation (CV = S.D./mean) was 18.4%. Normalized local SDH activity ranged from 0.16 to 1.94, with a CV of 21.8%, significantly exceeding measurement error (CV = 4.5%). Local blood flows and SDH activities did not vary among transmural sublayers of the left ventricle, but variation within each sublayer was considerable. In six of the seven pigs, local blood flow correlated (P < 0.05) with SDH activity, with correlation coefficients (r) ranging from 0.26 to 0.54 (for pooled data: r = 0.27, P < 0.0001). When expressed per gram dry weight, heterogeneity of SDH activity increased (P < 0.05), and here also local blood flow correlated with SDH activity in all pigs (for pooled data: r = 0.45, P < 0.0001). Hence, heterogeneity of mitochondrial capacity within cardiac muscle partly explains the heterogeneity of myocardial blood flow, even though myocardial perfusion at rest was studied in relation with a maximal enzyme rate. The low correlation coefficient clearly indicates that at resting workloads other factors also play a role.

Animals↗
PubMed1994

Effects of human growth hormone on fuel utilization and mineral balance in critically ill patients on full intravenous nutritional support.

PURPOSE: The effects of recombinant human growth hormone (GH) on fuel utilization, mineral and fluid balance in critically ill patients were studied. METHODS: Twenty patients requiring mechanical ventilation and receiving standard parenteral nutrition were studied. GH 0.1 mg/kg/day (n = 10) or placebo (n = 10) was administered as continuous intravenous infusion for 3 days. Plasma mineral levels, urinary nitrogen, and mineral excretion were measured. Indirect calorimetry was used to calculate energy production rate and fuel utilization. RESULTS: Insulin-like growth factor I concentrations increased: day 4 GH, 18.9 +/- 7.0 ng/mL; controls 11.6 +/- 3.2 ng/mL (P < .05). During GH administration, the nitrogen balance became zero, whereas it remained negative in controls (P = .03). Fuel utilization did not differ between the groups. Neither did oxygen consumption, carbon dioxide production, or the respiratory quotient (RQ). Nonprotein RQ showed a tendency to decrease in the GH group, whereas an increase was present in controls. Mineral balance improved in both groups. Phosphate balance improved by 250% in the GH group (P = .054). CONCLUSIONS: GH administration in critically ill patients reduces nitrogen loss and improves phosphate retention but does not have an important effect on fuel utilization.

APACHE↗
PubMed1994

A pilot study to evaluate the effects of C1 esterase inhibitor on the toxicity of high-dose interleukin 2.

In a pilot study six patients received 4 days' treatment with interleukin 2 (IL-2) [cumulative dose (CD) 264 +/- 26 x 10(6) IU m-2] and C1 esterase inhibitor (C1-INH) (loading dose 2,000 U, followed by 500-1,000 U twice daily). Toxicity was compared with that in patients given 4 days' treatment with standard (CD 66 +/- 12 x 10(6) IU m-2) or escalating-dose (CD 99 +/- 8 x 10(6) IU m-2) IL-2. IL-2-induced hypotension was equivalent and complement activation was less after IL-2 + C1-INH (C3a = 10.5 +/- 3.2 nmol l-1) than following standard (14.1 +/- 8.4 nmol l-1) or escalating-dose (18.3 +/- 2.9 nmol l-1) IL-2. This study demonstrates that C1-INH administration during IL-2 treatment is safe and warrants further study to evaluate its ability to ameliorate IL-2-induced toxicity.

Adult↗
PubMed1994

Frequencies of lipopolysaccharide core types in Escherichia coli strains from bacteraemic patients.

We have investigated the distribution of the various core types (R1, R2, R3, R4 and K-12) in 138 Escherichia coli isolates obtained from positive blood cultures. Rabbit antisera, raised against five rough strains expressing the respective core types, were made monospecific by extensive absorption. The reactivity of the antisera was tested in ELISA with bacterial cells that had been autoclaved for full exposure of core epitopes. One hundred and thirty strains could be typed directly, while eight strains required prior digestion with proteinase K for removal of cross-reactions. Ninety-four of the strains (68%) expressed the R1 type, and 9 (6.5%), 12 (8.7%), 7 (5.1%) and 3 (2.2%) strains expressed the R2, R3, R4 and K-12 core types, respectively. An R1R4 mixed core type, hitherto not yet described, was found in 13 (9.4%) strains. Results obtained with polyclonal antisera were in agreement with those obtained with monoclonal antibodies to the R1, R2 and R3 core types. Core typing may serve as an additional serological marker next to conventional typing of O-, H- and K-antigens.

Antibodies, Bacterial↗
PubMed1994

Binding studies of a monoclonal antibody specific for 3-deoxy-D-manno-octulosonic acid with a panel of Klebsiella pneumoniae lipopolysaccharides representing all of the O serotypes.

A monoclonal antibody (MAb) raised against Salmonella minnesota R595 and specific for alpha-3-deoxy-D-manno-octulosonic acid (alpha-Kdo) of the inner core was tested for binding to lipopolysaccharides (LPS) of Klebsiella pneumoniae. The MAb was tested in several assay systems (enzyme-linked immunosorbent assay, passive hemolysis, and inhibition of passive hemolysis) with a large panel (n = 23) of K. pneumoniae LPS representing all nine currently known O serotypes. MAb 20 showed reactivity with almost all O serotypes of K. pneumoniae LPS, and this reactivity could be inhibited by synthetic Kdo. This suggests an epitope in the cores of these Klebsiella LPS much like that in the inner core of LPS of S. minnesota. Large differences in reactivity between LPS of different strains belonging to the same O serotype were observed. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis of LPS followed by immunoblotting, reactivity of MAb 20 was observed only with the fast-moving fraction possibly representing the nonsubstituted core. No binding was seen with the high-molecular-weight fraction that contained core material substituted with several units of O-antigen building blocks. The chemical basis for these differences in reactivity remains to be established. As far as we know, this is the first report containing comprehensive immunochemical data on the LPS core of K. pneumoniae.

Antibodies, Monoclonal↗
PubMed1994

Delayed resolution of pulmonary oedema after cocaine/heroin abuse.

Pulmonary oedema lasting six days occurred in a 68 year old man after sniffing cocaine. He also had evidence of parenteral self-administration of heroin. Pulmonary microvascular filtration pressure and permeability were normal. Delayed resolution of the pulmonary oedema may have been caused by a cocaine-induced impairment of sodium and thus fluid transport across alveolar epithelium. Recognition may be important, since lowering filtration pressure with diuretics may not hasten resolution of oedema.

Aged↗
PubMed1994

Protective role of NO in the regional hemodynamic changes during acute endotoxemia in rats.

The role of NO during the first hour of endotoxemia is still controversial. To evaluate whether NO is protective or detrimental to the regulation of systemic blood pressure, cardiac output (CO), and organ perfusion in rats during acute endotoxemia, we have studied the effects of inhibition of NO synthesis. Thirty minutes after 0.1 mg NG-nitro-L-arginine (L-NNA; group L, n = 7, partial inhibition), 1 mg L-NNA (group H, n = 6, complete inhibition), or saline (group E, n = 7) intravenous infusion, anesthetized volume-loaded rats were infused with endotoxin Escherichia coli O127:B8 (8 mg.kg-1 x h-1) from time (t) = 0 to 60 min. Organ blood flow was measured with radioactive microspheres. In group H, at time 0, CO was lower than in group E (by -29%; P < 0.05), and systemic vascular resistance (SVR) was higher than in groups E and L (by 72 and 51%, respectively; P < 0.05). Perfusion of the pancreas, stomach, intestines, and kidney was lower (P < 0.05) and corresponding organ vascular resistance (OVR) higher (P < 0.05) in group H than in groups E and L (except kidney in group L). At t = 60 min, in groups H and L, CO was lower (by -45 and -26%, respectively; P < 0.05) and SVR was higher (by 112 and 54%, respectively; P < 0.05) than in group E. In group L only blood flow to the heart, pancreas, intestines, and kidney was significantly lower than in group E, and corresponding OVR was higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Initial studies on the administration of C1-esterase inhibitor to patients with septic shock or with a vascular leak syndrome induced by interleukin-2 therapy.

Activation of the complement and contact systems occur in patients with septic shock and is associated with a poor outcome. Activation of both systems is regulated by a common inhibitor, C1-esterase inhibitor (C1-Inh). Functional levels of C1-Inh are normal or slightly decreased in septic patients although this inhibitor is an acute phase protein. Moreover, an increased turn-over of C1-Inh in sepsis likely occurs since levels of proteolytically inactivated ("modified") C1-Inh are increased in this syndrome. One may therefore postulate that in sepsis there is a relative deficiency of C1-Inh. Here we will summarize our preliminary studies in 11 patients with septic shock, who received high doses of C1-Inh for up to 5 days. Activation of complement and contact systems also occurs in "a human model for septic shock" i.e., the vascular leak syndrome (VLS) induced by immunotherapy with the cytokine interleukin-2 (IL-2). The similarity between VLS and sepsis is not only reflected by similar patterns of complement and contact activation, but also by comparable hemodynamic and biochemical changes, and by the involvement of a number of other inflammatory mediators, such as the release of pro-inflammatory cytokines, and activation of coagulation and fibrinolysis and of neutrophils. Here we will also summarize our initial studies of the effect of C1-Inh administration to 6 patients with the VLS induced by IL-2. Our results indicate that high doses of C1-Inh can be safely administered to patients with septic shock or with the VLS, and may attenuate complement and contact activation in these conditions. Whether this therapy may reduce mortality and or morbidity of either syndrome has to be established by double-blind controlled studies.

Blood Coagulation↗