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Biomedical subjects

C J van der Linden

Publications and source records attributed to C J van der Linden.

At least 19 recordsLinked to original sources
PubMed2004

Modulation of adhesion molecule expression on endothelial cells after induction by lipopolysaccharide-stimulated whole blood.

The relative contribution of the pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 beta and the lipopolysaccharide (LPS)-induced pathways that result in endothelial activation during sepsis are not fully understood. We have examined the effects of plasma obtained from LPS-treated human whole blood on the expression of E-selectin and intercellular adhesion molecule-1 (ICAM-1) on human endothelial cells. Stimulation of blood with 10 pg/ml of LPS is sufficient to produce plasma that induces E-selectin and ICAM-1 expression, while direct induction by LPS alone requires a 100-fold higher concentration. Characteristics for the plasma-induced adhesion molecule expression were similar to the LPS-induced production of TNF-alpha and IL-1 beta in blood. A complete inhibition of E-selectin and ICAM-1 expression was observed when antibodies against TNF-alpha and IL-1 beta were added to plasma prior to the incubation to endothelial cultures. Significant inhibition was even observed if antibodies were added to the cultures up until 3 h after LPS-conditioned plasma. The plasma-induced adhesion molecule response could also be prevented with inhibitors of nuclear factor (NF)-kappaB, such as pyrollidine dithiocarbamate. These findings emphasize the central role of TNF-alpha and IL-1 beta in LPS-induced endothelial activation and suggest that simultaneous neutralization of these cytokines or their common pathways may, even after the initial stimulus, prevent endothelial response during sepsis.

Cell Adhesion Molecules↗
PubMed2000

Permeability characteristics of human endothelial monolayers seeded on different extracellular matrix proteins.

OBJECTIVE: To investigate whether endothelial monolayer permeability changes induced by inflammatory mediators are affected by the extracellular matrix protein used for cell seeding. METHODS: Human umbilical venular endothelial cells (HUVEC) were grown to confluent monolayers on membranes coated with either collagen, fibronectin or gelatin. The permeability to albumin and dextran was then assessed, both under normal conditions and after treatment with tumor necrosis factor-alpha (TNF-alpha) and bacterial lipopolysaccharide (LPS). RESULTS: With any of the three protein coatings, tight junctions were formed all over the monolayers. The permeability of the coated membranes to albumin and dextran was reduced strongly by confluent monolayers; the relative reduction was similar for the three matrix proteins used. Pre-incubation of the monolayers with either TNF-alpha or LPS increased permeability dose dependently. However, the relative increase due to either treatment was independent of the protein used for membrane coating. CONCLUSION: The extracellular matrix protein used for initial seeding of endothelial cultures plays a minor role in determining the permeability changes induced in HUVEC monolayers by inflammatory mediators.

Cell Membrane Permeability↗
PubMed1998

Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil.

Experimental studies indicate that anastomotic healing in the intestine is compromised by the immediate postoperative administration of 5-fluorouracil and levamisole. Since fibroblast functions are crucial to healing, we investigated the effects of (combinations of) both drugs on proliferation and collagen synthesis of rat skin fibroblasts in vitro. Proliferation was measured in actively dividing cells by cellular [3H]thymidine uptake and collagen synthesis in non-dividing cells by [3H]proline incorporation into collagenase-digestible protein. 5-Fluorouracil strongly and significantly (P < 0.05) reduced DNA synthesis and collagen synthesis at concentrations of 1 microM or more. The latter effect was not specific for collagen since total protein production was affected similarly. Both effects depended on the duration of exposure to the drugs. Levamisole also inhibited fibroblast proliferation dose-dependently, but less effectively than 5-fluorouracil: 50% inhibition was observed at approximately 0.1 mM. Collagen synthesis was unaffected by levamisole. If levamisole was added together with a low (0.1 microM) concentration of 5-fluorouracil, which in itself did not decrease thymidine incorporation, levamisole's antiproliferative effects became apparent at concentrations as low as 1 microM. A similar effect, but at a much higher concentration (1 mM) was noted on fibroblast collagen synthesis. These results indicate that levamisole potentiates 5-fluorouracil effects in fibroblast cultures and that direct effects of these drugs, alone or in combination, on fibroblast proliferation and collagen synthesis may be responsible for their negative influence on wound repair.

Adjuvants, Immunologic↗
PubMed1997

Differential induction of pro- and anti-inflammatory cytokines in whole blood by bacteria: effects of antibiotic treatment.

The in vitro production of interleukin-1beta (IL-1beta), IL-6, and the IL-1 receptor antagonist (IL-1ra) in whole blood upon stimulation with different bacterial strains was measured to study the possible relationship between disease severity and the cytokine-inducing capacities of these strains. Escherichia coli, Neisseria meningitidis, Neisseria gonorrhoeae, Bacteroides fragilis, Capnocytophaga canimorsus, Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae, and Streptococcus pyogenes induced the cytokines IL-1beta, IL-6, and IL-1ra. Gram-negative bacteria induced significantly higher levels of proinflammatory cytokine production than gram-positive bacteria. These differences were less pronounced for the anti-inflammatory cytokine IL-1ra. In addition, blood was stimulated with E. coli killed by different antibiotics to study the effect of the antibiotics on the cytokine-inducing capacity of the bacterial culture. E. coli treated with cefuroxime and gentamicin induced higher levels of IL-1beta and IL-6 production but levels of IL-1ra production similar to that of heat-killed E. coli. In contrast, ciprofloxacin- and imipenem-cilastatin-mediated killing showed a decreased or similar level of induction of cytokine production as compared to that by heat-killed E. coli; polymyxin B decreased the level of production of the cytokines.

Anti-Bacterial Agents↗
PubMed1997

Introduction of a computerised protocol in clinical practice: is there anything to gain?

OBJECTIVES: To assess the potential benefit of a protocol for the diagnostic work-up and management of patients with obstructive jaundice, by comparing its recommendations with the policies actually followed in patients and to compare local expertise with diagnostic and therapeutic procedures with that described in published reports. DESIGN: A retrospective analysis of patients' records. SETTING: University hospital, The Netherlands. SUBJECTS: 49 consecutive patients who presented to the departments of internal medicine and surgery between June 1990 and June 1992 with serum alkaline phosphatase activities > 125 mumol/L, and serum bilirubin concentrations > 17 mumol/L. MAIN OUTCOME MEASURES: The proportions of diagnostic and therapeutic decisions that deviated from the recommendations, and the success rates of diagnostic and therapeutic procedures. RESULTS: In patients with bile duct stones the treatment strategies did not deviate from those recommended in the protocol. In patients with cancer 38 (30%) of the 128 diagnostic decisions and 4 (11%) of the 37 therapeutic decisions deviated from the protocol. Success rates of all diagnostic investigations were comparable with those reported, and success rates of endoscopic biliary drainage tended to be lower than those reported. CONCLUSIONS: The introduction of a protocol for the diagnostic work-up of patients with obstructive jaundice may reduce unnecessary investigations and diagnostic omissions by half. Because local expertise of some of the procedures seems to be significantly less than reported elsewhere it may be necessary to modify the protocol to better fit local circumstances.

Aged↗
PubMed1996

Impact of a protocol processing system (ProtoVIEW) on clinical behaviour of residents and treatment.

A protocol processing system (ProtoVIEW), containing therapeutic trauma protocols, was used in the Accident and Emergency (A and E) department for a period of 7 months to investigate the impact of automated protocols on firstly, medical decision making of physicians and secondly, on quality of treatments eventually received by the patients. A randomized controlled trial showed that mandatory use of the system led to a more uniform working strategy while fracture treatment only seemed to improve in a subgroup of patient for whom residents established a correct diagnosis.

Adolescent↗
PubMed1996

Effects of a supportive protocol processing system (ProtoVIEW) on clinical behaviour of residents in the accident and emergency department.

A randomized two period crossover trial was performed at the Accident and Emergency (A & E) department of the University Hospital in Nijmegen (The Netherlands). We assessed what the impact was of (mandatory) consultation of a protocol for the management of isolated traumas on treatment decisions of residents. All eight surgical residents who regularly worked in the A & E department participated in the trial. All patients who entered the A & E department between October 13, 1992 and June 9, 1993, of age 16 years or older with an isolated fracture without concomitant lesions were admitted to the study. During the experimental periods, the management protocol was available on computer (using ProtoVIEW) and during the control periods on paper. Main measurements were treatment adjustments made by residents (after consulting different information sources), and their opinion about ProtoVIEW as an information source assessed by means of a questionnaire. When protocol consultation was mandatory, residents changed their treatments almost four times more often towards the protocol than during the control periods (P = 0.01 Chi-square test). Most residents found ProtoVIEW easy to use, liked it as a useful training source while half of them said they would use the system in daily clinical practice. We conclude that mandatory protocol consultation using ProtoVIEW influenced protocol adherence positively.

Attitude↗
PubMed1996

The effects of 5-fluorouracil and interferon-alpha on early healing of experimental intestinal anastomoses.

The continuing search for effective adjuvant therapy after resection of intestinal malignancies has prompted a growing interest in both immediate post-operative regional chemotherapy and the combination of 5-fluorouracil (5-FU) and interferon-alpha as drugs of choice. We have compared the effects of both compounds, alone and together, on early healing of intestinal anastomoses. Four groups (n = 26 each) of rats underwent resection and anastomosis of both ileum and colon: a control group and three groups receiving intraperitoneal 5-FU, interferon-alpha or both on the day of surgery and the next 2 days. Animals were killed 3 or 7 days (n = 10 each) after operation in order to measure anastomotic strength and hydroxyproline content. The remaining six animals in each group were used to study anastomotic collagen synthetic capacity at day 3. Three days after operation, ileal anastomotic bursting pressure was lowered by 37% in the 5-FU/interferon-alpha group (P = 0.0104). At day 7, anastomotic breaking strength was reduced significantly in ileum (P = 0.0221) and colon (P = 0.0054) of the 5-FU/interferon-alpha group and in colon of the interferon-alpha group (P = 0.0221). Collagen synthetic capacity was strongly suppressed by 5-FU but not by interferon-alpha. However, no differences in anastomotic hydroxyproline content were observed between groups at both days 3 and 7. Thus, post-operative use of interferon-alpha, in particular in combination with 5-FU, may be detrimental to anastomotic repair in the intestine.

Anastomosis, Surgical↗
PubMed1996

Interleukin-6 and its soluble receptor during acute meningococcal infections: effect of plasma or whole blood exchange.

OBJECTIVES: To determine the pattern of the soluble interleukin (IL)-6 receptor during acute meningococcal infections and recovery phase, and to measure the effect of plasma or whole blood exchange on the plasma concentrations of these mediators. DESIGN: Prospective, descriptive patient study. SETTING: University hospital intensive care unit. PATIENTS: Patients with bacteriologically proven meningococcal infections were entered in the study. Three group were formed: a) patients with meningitis without shock (group A); b) patients with meningitis and shock (group B); and c) patients with shock only (group C). INTERVENTIONS: Part (n = 9) of the patients with shock underwent plasma or whole blood exchange. MEASUREMENTS AND MAIN RESULTS: Serum concentrations of interleukin-6 and soluble IL-6 receptors were determined sequentially during the acute and recovery phases. Peak concentrations of IL-6 were highest in group C, followed by group B and group A. Soluble IL-6 receptor concentrations showed an opposite pattern and were all below normal. Soluble IL-6 receptor concentrations were negatively correlated with the IL-6 concentrations. During recovery, IL-6 rapidly decreased and soluble IL-6 receptors increased to supranormal concentrations, after which concentrations returned to normal. Plasma or whole blood exchange did not significantly influence IL-6 concentrations but did increase the soluble IL-6 receptor concentration directly after an exchange session followed by a rapid decrease. CONCLUSIONS: Soluble IL-6 receptor concentrations are low in acute meningococcal infections. Plasma or whole blood exchange temporarily increases these concentrations. It needs to be determined whether the effect of this therapy is beneficial to the patient.

Acute Disease↗
PubMed1996

Treatment with the platelet-activating factor antagonist TCV-309 in patients with severe systemic inflammatory response syndrome: a prospective, multi-center, double-blind, randomized phase II trial.

In a prospective randomized, double-blind, placebo-controlled clinical study, the safety and efficacy of the platelet-activating factor antagonist TCV-309 in the treatment of systemic inflammatory response syndrome was studied. In total 29 patients were treated with 1.0 mg/kg TCV-309 twice daily during 7 days or with placebo. Study parameters were as follows: adverse events, 28 and 56 day all cause mortality, multi-organ failure scores, and the inflammatory mediators tumor necrosis factor, interleukin 6, interleukin 8, and soluble E-selectin. There was no difference in number and severity of adverse events between TCV-309- and placebo-treated patients. Day 28 and day 56 mortality was similar in both groups (day 56: 7/12 TCV-309 vs. 9/16 placebo, NS). Pulmonary and hematological failure scores improved significantly in TCV-309-treated patients (p < .05). There was no difference in inflammatory mediator levels between TCV-309- and placebo-treated patients. Treatment with TCV-309 appears to be safe in patients with systemic inflammatory response syndrome and does improve organ failure significantly.

Adult↗
PubMed1995

Retinol may promote fluorouracil-suppressed healing of experimental intestinal anastomoses.

OBJECTIVES: To examine the effects of perioperative administration of fluorouracil on healing variables of internal anastomoses and to explore ways to promote repair under these conditions. DESIGN: Seven-day, prospective randomized experimental trial. SETTING: Animal research laboratory. ANIMALS: Male young-adult Wistar rats after resection and anastomosis of both ileum and colon. INTERVENTIONS: Random assignment to groups receiving placebo, daily fluorouracil (20 mg/kg per day, intraperitoneally), daily fluorouracil plus retinol palmitate (5000 IU/kg per day, orally), daily fluorouracil plus interleukin-2 (2 x 10(6) IU/kg per day, subcutaneously), or daily fluorouracil plus granulocyte macrophage colony-stimulating factor on the first 4 days after operation (20 micrograms/kg per day, intraperitoneally. MAIN OUTCOME MEASURES: Anastomotic bursting pressure, breaking strength, hydroxyproline content, and ex vivo collagen synthetic capacity. RESULTS: Administration of fluorouracil decreased anastomotic breaking strength by more than 40% and caused a shift in bursting site from outside to within the suture line. It also lowered anastomotic hydroxyproline content. The capacity for collagen synthesis, which was greatly enhanced in 4-day-old anastomoses from the control group, was significantly (P < .05) and specifically reduced. Concomitant administration of retinol resulted in restoration of strength and hydroxyproline content, particularly in the ileum. Interleukin-2 and granulocyte macrophage colony-stimulating factor did not improve fluorouracil-suppressed repair: both wound strength and collagen content were similar in the fluorouracil, fluorouracil/interleukin-2, and fluorouracil/granulocyte macrophage colony-stimulating factor groups. CONCLUSION: Intraperitoneal administration of fluorouracil, delivered from the day of operation onward, severely reduces anastomotic strength at the end of the first postoperative week. This negative effect may be prevented by oral administration of retinol.

Anastomosis, Surgical↗
PubMed1995

Post-operative levamisole may compromise early healing of experimental intestinal anastomoses.

There exists growing interest in immediate post-operative local adjuvant therapy after resection of intestinal malignancies. It is therefore necessary to assess it potential effect on the healing of intestinal anastomoses. Five groups (n = 20) of rats underwent resection and anastomosis of both ileum and colon: a control group and four experimental groups receiving intraperitoneal 5-fluorouracil (5-FU), 5-FU plus leucovorin, 5-FU plus levamisole or levamisole alone, on the day of surgery and the next 2 days. Animals were killed 3 or 7 days after operation. Another three groups (n = 6) of animals were used to compare anastomotic collagen synthetic capacity in control rats or rats receiving 5-FU or 5-FU plus levamisole. On the third post-operative day, the average anastomotic bursting pressure in the 5-FU/levamisole group was reduced by 36% as compared with the control group, both in ileum (P = 0.02) and in colon (P = 0.01). Values in the other groups were similar to those in the control group. Anastomotic breaking strength was significantly (P < 0.025) lowered in the ileum from the levamisole group at both days 3 and 7. Anastomotic collagen synthetic capacity was strongly reduced in the 5-FU and 5-FU/levamisole groups. However, there was no significant difference between the control group and the four experimental groups with regard to anastomotic hydroxyproline concentration and content, either 3 or 7 days after operation. Thus, limited use of levamisole, alone or in combination with intraperitoneal 5-FU, may compromise intestinal healing.

Anastomosis, Surgical↗
PubMed1995

Circulating interleukin-6 receptor in patients with sepsis syndrome.

Concentrations of interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), and soluble tumor necrosis factor receptor (sTNFR) p55 and p75 were measured in 25 patients with sepsis syndrome. Sequential blood samples were drawn from patients during a 7-h period. IL-6 concentrations were 34-763,000 pg/mL; they were higher in nonsurvivors than survivors, but the difference was not statistically significant. In septic patients, the median sIL-6R concentration was significantly lower than in 19 healthy volunteers (43 vs. 80 ng/mL). sIL-6R concentrations in survivors were not significantly different than those in nonsurvivors. There was a negative correlation between IL-6 and sIL-6R in septic patients (r = -.72). In patients with moderately impaired renal function, sIL-6R levels were not affected, but the concentrations of sTNFRs were significantly higher.

Adolescent↗
PubMed1994

Soluble interleukin 6 receptor in biological fluids from human origin.

OBJECTIVE: measurement of baseline soluble interleukin 6 receptor (sIL-6R) and interleukin 6 (IL-6) levels in biological fluids in non-pathological conditions. SUBJECTS AND MATERIALS: Blood and urine were obtained from healthy volunteers. Cerebrospinal fluid (CSF) and synovial fluid (SF) were obtained from patients during spinal puncture and athroscopy, respectively. Only CSF and SF of patients with proven non-pathological conditions were used in this study. Both sIL-6R and IL-6 were measured using ELISAs. It was shown that neither did sIL-6R interfere with the IL-6 ELISA nor did IL-6 interfere in the sIL-6R ELISA. Moreover, addition of recombinant sIL-6R to the IL-6 bio-assay (B9) did not influence IL-6 recovery. RESULTS: using our sIL-6R ELISA we found baseline levels for sIL-6R in serum of 76.6 +/- 19.3 ng/ml in serum and 3.7 +/- 1.3 ng/ml in urine. In non-pathological conditions sIL-6R concentrations in CSF are 1.6 +/- 0.4 ng/ml, and in SF 11.6 +/- 3.3 ng/ml, while IL-6 concentrations are below detectable ranges in these fluids. CONCLUSIONS: sIL-6R levels are detectable in serum, urine, CSF and SF during non-pathological conditions. sIL-6R levels in serum outrange levels in CSF, urine and SF and large interindividual differences in baseline concentrations for sIL-6R exist.

Biological Assay↗
PubMed1994

Increased plasma concentrations of soluble tumor necrosis factor receptors in sepsis syndrome: correlation with plasma creatinine values.

OBJECTIVES: Tumor necrosis factor (TNF) is an important mediator in the complex pathophysiology of sepsis syndrome. Although a positive correlation with mortality rate has been demonstrated, TNF has not been found consistently in sepsis. Since prolonged increases in soluble TNF receptor concentrations were demonstrated after endotoxin and TNF administration, we investigated whether the measurement of TNF receptor concentrations could provide a better indicator of disease than plasma TNF and interleukin (IL)-6 concentrations. DESIGN: Prospective analysis. SETTING: General intensive care unit (ICU) of a university hospital. PATIENTS: Twenty-six patients with sepsis syndrome and proven bacteremia. MEASUREMENTS AND MAIN RESULTS: Plasma peak concentrations of the soluble 55-kilodalton molecular weight TNF receptor were significantly higher (p < .005) in nonsurvivors compared with survivors of sepsis syndrome, whereas the difference in peak concentrations of the soluble 75-kilodalton TNF receptor did not reach significance (p = .06). In contrast to TNF peak concentrations (p = .14), significantly higher (p < .05) IL-6 peak concentrations were measured in nonsurvivors. Besides the positive correlation between the soluble 55-kilodalton TNF receptor and the soluble 75-kilodalton TNF receptor (r2 = .68; p < .0001), peak concentrations of both soluble 55-kilodalton TNF receptor and 75-kilodalton TNF receptor correlated significantly with plasma creatinine values, an indicator of renal function (r2 = .60; p < .0001 and r2 = .44; p < .001, respectively). Plasma creatinine concentrations were significantly higher in nonsurvivors (p < .001). CONCLUSIONS: In the population studied, plasma-soluble TNF receptor concentrations correlated with outcome as well as with plasma creatinine concentrations. The data presented suggest that increased plasma-soluble TNF receptor concentrations in patients with sepsis syndrome are merely the result of renal failure complicating sepsis, and are similarly correlated with mortality rate.

Adult↗
PubMed1994

Effect of hemodialysis on peripheral blood monocyte tumor necrosis factor-alpha, interleukin-6, and interleukin-8 secretion in vitro.

The influence of blood-membrane interaction on human peripheral blood monocyte tumor necrosis factor-alpha (TNF), interleukin-6 (IL-6), and interleukin-8 (IL-8) secretion was measured during hemodialysis of end-stage renal disease patients by in vitro stimulation of whole blood with lipopolysaccharide. Monocyte TNF and IL-6 secretion in vitro was reduced 30 min after start of dialysis session. In contrast, cellular IL-8 secretion did not change during hemodialysis. Comparison of the results of three different membranes indicates that the bioincompatibility of the dialysis membrane was reflected in both leukocytopenia and reduction of cellular TNF secretion. During treatment of normal whole blood in an ex vivo dialysis closed-loop circuit, the ability of monocytes to release TNF, IL-6, and IL-8 in vitro remained constant. This indicates that the reduced IL-6 and TNF secretion during standard hemodialysis was not due to a direct effect of contact between dialysis membranes and monocytes, but rather was a result of redistribution within the patients' leukocyte pool.

Adult↗