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Dive into the research topics where Lambertus G. Thijs is active.

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Featured researches published by Lambertus G. Thijs.


The Lancet | 1998

Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma

Alexander P. J. Houdijk; Emmy R Rijnsburger; Jaap Jansen; R. I. C. Wesdorp; Jeffery K Weiss; Mark Anthony Mccamish; Tom Teerlink; Stephan Gm Meuwissen; Henk J. Th. M. Haarman; Lambertus G. Thijs; Paul A. M. van Leeuwen

BACKGROUNDnInfections are an important cause of morbidity and mortality in patients with multiple trauma. Studies in both animals and human beings have suggested that glutamine-enriched nutrition decreases the number of infections.nnnMETHODSnPatients with multiple trauma with an expected survival of more than 48 h, and who had an Injury Severity Score of 20 or more, were randomly allocated glutamine supplemented enteral nutrition or a balanced, isonitrogenous, isocaloric enteral-feeding regimen along with usual care. Each patient was assessed every 8 h for infection, the primary endpoint. Data were analysed both per protocol, which included enteral feeding for at least 5 days, and by intention to treat.nnnFINDINGSn72 patients were enrolled and 60 received enteral feeding (29 glutamine-supplemented) for at least 5 days. Five (17%) of 29 patients in the glutamine-supplemented group had pneumonia compared with 14 (45%) of 31 patients in the control group (p<0.02). Bacteraemia occurred in two (7%) patients in glutamine group and 13 (42%) in the control group (p<0.005). One patient in the glutamine group had sepsis compared with eight (26%) patients in the control group (p<0.02).nnnINTERPRETATIONnThere was a low frequency of pneumonia, sepsis, and bacteraemia in patients with multiple trauma who received glutamine-supplemented enteral nutrition. Larger studies are needed to investigate whether glutamine-supplemented enteral nutrition reduces mortality.


Journal of Immunological Methods | 1985

An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region

Ben J. Appelmelk; A.M.J.J. Verweij-van Vught; D. M. Maclaren; Lambertus G. Thijs

Bovine serum albumin was complexed with the core antigens of either Escherichia coli J5 LPS, Salmonella minnesota R595 LPS or E. coli lipid A. These core-BSA complexes were used for solid-phase coating in ELISAs for anti-core antibodies. Antibodies, binding to various parts of the core region were easily quantified in a single experimental set-up, which was hitherto not possible. The ELISA has only 3 incubation steps and is not costly as only moderate amounts of the core antigens (i.e., 1 microgram per test) were needed for coating. The sensitivity proved to be excellent and the complexes were biologically fully active (compared to native, smooth LPS), which make them suitable for the screening (after fusion) of monoclonal anti-core antibodies. Another possible application is the large-scale screening of blood-bank sera in order to find samples with a high anti-core antibody content.


Microvascular Research | 1987

Changes in regional plasma extravasation in rats following endotoxin infusion

A.A. van Lambalgen; G. C. van den Bos; Lambertus G. Thijs

Regional differences in plasma extravasation during endotoxin shock in rats and a possible relationship with changes in regional blood flow were studied with radioactive isotopes (125I-HSA, 51Cr-labeled red blood cells, microspheres) in anesthetized rats (pentobarbital). Shock was induced by intravenous infusion of endotoxin (Eschericia coli; 10 mg X kg-1) for 60 min (starting at t = 0); at t = 120 min, the experiments were terminated. These rats (n = 8) were compared with time-matched control rats (n = 8). A third group (rats killed 7.5 min after injection of 125I-HSA, i.e., no extravasation; n = 8) served as baseline. The amount of plasma extravasated in 2 hr of endotoxin shock was significantly increased over control values in skin (by 67%), colon (88%), skeletal muscle (105%), stomach (230%), pancreas (300%), and diaphragm (1300%). Losses of 125I-HSA into intestinal lumen and peritoneal cavity had also increased over control values by 146 and 380%, respectively. Blood flow was compromised in most organs except heart and diaphragm. Extravasation when normalized for total plasma supply was correlated with total blood supply; the more the blood supply decreased, the higher the normalized extravasation. In the diaphragm, however, blood supply and plasma leakage increased together. Decreased blood supply and plasma extravasation may be related but they could also be simultaneously occurring independent phenomena with a common origin.


Journal of Critical Care | 1993

Organ blood flow and distribution of cardiac output in dopexamine- or dobutamine-treated endotoxemic rats.

Antoine A. van Lambalgen; Annemieke A. van Kraats; M. F. Mulder; Gerard C van den Bos; T. Teerlink; Lambertus G. Thijs

Endotoxemia causes a decrease of blood flow to most organs. If this could be prevented, chances of survival might improve. In endotoxemic rats, we studied the effect of a therapeutic infusion of dopexamine (dopaminergic, beta 2-adrenergic) on blood flow and percentage of the cardiac output distributed to heart, brain, hepatic artery, stomach, intestines, spleen, pancreas, kidneys, adrenals, diaphragm, skeletal muscle, and skin. Dopexamine action was compared with that of dobutamine (beta 1-adrenergic). Endotoxin shock was induced in 28 rats with infusion of 8 mg/kg Escherichia coli O127:B8 endotoxin from 0 to 60 minutes; the rats were then divided into 3 groups, which received from 60 to 135 minutes of an infusion of saline (ES; n = 10), dopexamine hydrochloride (DX, 3 x 10(-8) mol/kg.min; n = 10) or dobutamine (DB, 10(-7) mol/kg.min; n = 8). A fourth group served as time-matched controls (C, saline from 0 to 135 minutes; n = 8). In the untreated endotexemic rats, cardiac output decreased and organ blood flow decreased except in the diaphragm, heart, and brain; the percentage of the cardiac output to those organs increased. Dopexamine and dobutamine similarly improved cardiac output in endotoxemic rats. All organs benefitted to the same extent from the increased cardiac output. Therapeutic infusion of dopexamine during endotoxemia did not favor flow to any particular organ; redistribution of cardiac output changed little after administration of dopexamine, and its effects were not significantly different from those of dobutamine.


Shock | 2001

Arginase release from red blood cells: possible link in transfusion induced immune suppression?

Hubert A. Prins; Alexander P. J. Houdijk; Robert J. Nijveldt; Tom Teerlink; Peter Huygens; Lambertus G. Thijs; Paul A. M. van Leeuwen

Arginine stimulates lymphocyte function and is degraded by arginase, an enzyme that is abundantly present in red blood cells. Arginase impairs lymphocyte function and responses in vitro. Leakage of arginase from stored red blood cells may be involved in the lymphocyte dysfunction associated in allogenic blood transfusion. In the present study, arginase activity was determined in bags of red cells stored for transfusion. Buffy coat depleted red blood cells were obtained routinely from four healthy donors and stored in bags for a maximum period of five weeks at 4 degrees C. The bags were sampled for determination of arginase, lactate dehydrogenase, and potassium. In addition, a random sample of 36 bags of red blood cells about to be transfused to patients were studied. Levels of arginase, lactate dehydrogenase, and potassium showed a time dependent increase in the bags of the four donors. This time dependent increase in arginase activity could be confirmed in the additional bags sampled (P < 0.0001, r = 0.78). The results for the first time show that arginase is released from red blood cells during storage for transfusion. Arginase infusion may play an important role in the immune suppression observed after blood transfusion.


Journal of Medical Microbiology | 1988

Production and characterisation of mouse monoclonal antibodies reacting with the lipopolysaccharide core region of gram-negative bacilli.

Ben J. Appelmelk; A. M. J. J. Verweij-Van Vught; J.J. Maaskant; W.F. Schouten; A. J. R. De Jonge; Lambertus G. Thijs; D. M. Maclaren

Monoclonal antibodies to the lipopolysaccharide (LPS) core region were produced by immunising mice with Escherichia coli strain J5 (chemotype Rc). One of these bound to the deepest part of the core, i.e., Lipid A, and reacted with other heat-killed but not live gram-negative bacilli, including E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Eight other monoclonal antibodies, binding to the terminal glucose residue of Rc LPS, reacted with live cells of E. coli strains only. Thus, the O antigen does not necessarily render the core inaccessible to antibody. However, despite binding to live bacteria, these monoclonal antibodies neither enhanced phagocytic killing, nor protected mice from dying from gram-negative infection or endotoxaemia. It is concluded that antibodies reacting with the most immunodominant parts of the J5 core are not protective.


Shock | 2001

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.

Catharina Meijer; Marinus J. Wiezer; Erik C. Hack; Petra G. Boelens; Nancy Wedel; Sybren Meijer; Robert J. Nijveldt; Markwin G. Statius Muller; Theo Wiggers; F.A.N. Zoetmulder; Inne H.M. Borel Rinkes; Miguel A. Cuesta; Dirk J. Gouma; Cornelis J. H. van de Velde; Hugo W. Tilanus; Michel Scotté; Lambertus G. Thijs; Paul A. M. van Leeuwen

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.


Shock | 1998

Gut endotoxin restriction improves postoperative hemodynamics in the bile duct -ligated rat

Alexander P. J. Houdijk; Anton A. van Lambalgen; Lambertus G. Thijs; Paul A. M. van Leeuwen

Background Postoperative hemodynamic disturbances in obstructive jaundice are associated with complications such as shock and renal failure. Gut-derived endotoxemia may underlie these complications. Recently, we have shown that cholestyramine treatment prevents gut-derived endotoxemia in bile duct-ligated (BDL) rats (Houdijk APJ, Boermeester MA, Wesdorp RIC, Hack CE, van Leeuwen PAM: Tumor necrosis factor unresponsiveness following surgery in bile duct-ligated rats. Am J Physiol 271: G980-G986, 1996). Methods: The effect of cholestyramine on systemic hemodynamics and organ blood flows after a laparotomy was studied in 2 wk BDL rats using radioactive microspheres. Results: Compared with sham-operated rats, postoperative BDL rats had 1) lower blood pressure (p < .05) and heart rate (p < .001) with higher cardiac output (p < .05), 2) lower splanchnic blood flow (p < .05), 3) lower renal blood flow (p < .01), and 4) higher splanchnic organ and renal-vascular resistances. Cholestyramine treatment in BDL rats prevented the postoperative decrease in blood pressure by increasing cardiac output (p < .01). In addition, cholestyramine maintained splanchnic blood flow at sham levels (p < .05). Furthermore, cholestyramine also prevented the fall in renal blood flow after surgery in BDL rats. Conclusion: Gut endotoxin restriction using cholestyramine treatment maintained normal blood pressure, improved splanchnic blood flow, and completely prevented the fall in renal blood flow in BDL rats. Reducing the gut load of endotoxin in patients with obstructive jaundice scheduled for abdominal surgery may prevent postoperative hemodynamic complications.


Shock | 1998

Pharmacokinetics of a recombinant amino terminal fragment of bactericidal/permeability increasing protein (rBPI21) after liver surgery in rats and humans.

Marinus J. Wiezer; Sterre I. Langendoen; Catherina Meijer; Robert J. Bauer; Mark L. White; Stephen F. Carroll; Sybren Meyer; Lambertus G. Thijs; Paul A. M. van Leeuwen

ABSTRACT Major liver resections are associated with considerable morbidity and mortality. Gut-derived bacteria and bacterial endotoxin (LPS) are considered to play a central role in the pathophysiology of these complications. Like human BPI, rBPl21 binds to LPS from Gram-negative bacteria. By binding and clearing of LPS, rBPI21 can inhibit a number of endotoxin-induced humoral and cellular responses. Because of this capacity, rBPI21 could partially compensate for the loss of hepatic mononuclear phagocytic system function after liver resection. However, the liver is also thought to be an important organ for the clearance of BPI, and reduction of liver mass could result in a decreased clearance and exceedingly high plasma levels of rBPI21. In this study we therefore investigated the pharmacokinetics of rBPI21 in rats and in patients undergoing a major liver resection. Rats were administered an intravenous (i.v.) bolus of rBPI21 after undergoing a 60% or 80% hepatectomy (with sham-operated controls). Patients undergoing a hemihepatectomy and healthy volunteers received rBPI21 or placebo by continuous i.v. infusion for 48 h. Plasma concentrations were measured by sandwich ELISA. In rats, 60% hepatectomy did not consistently change the clearance of rBPI21, whereas 80% hepatectomy decreased the clearance of rBPI21 severalfold. In hemihepatectomized patients, the clearance of rBPI21 after major hepatectomy was also slower, when compared with healthy volunteers, but this difference had disappeared within 24 h. Our data indicate that the administration of rBPI21 in patients undergoing liver resection is well tolerated and does not result in exceedingly high plasma levels. Additional studies on the efficacy of rBPI21 in the prevention of complications after hepatectomy are needed.


Journal of Critical Care | 1987

Noninvasive assessment of regional albumin extravasation in porcine septic shock

A.B.Johan Groeneveld; G. A. K. Heidendal; Willem den Hollander; Jos J.P. Nauta; Lambertus G. Thijs

In order to study noninvasively the regional distribution of changes in microvascular albumin flux in septic shock, 131I human serum albumin and 98mTc red blood cells were injected IV into anesthetized pigs randomized to receive saline (n = 4) or live E. coli bacteria 3 × 108 × kg−1 IV (n = 8). Images of thorax, abdomen, and left hindlimb were obtained using a gamma camera and a computer. Septic pigs developed pulmonary hypertension and low cardiac output circulatory shock. Hematocrit rose and plasma colloid osmotic pressure fell. Regions of interest were drawn in the 99mTc images. For each region we calculated an albumin leak index. The albumin leak index over the lungs was higher in sepsis than in controls (1.62 ± 0.42 × 10−3 v 0.45 ± 0.05 × 10-3 × min−1, P < .005), even when divided by the pulmonary intravascular filtration pressure, incorporating hydrostatic and colloid osmotic pressures (P < .01). The index was also higher in abdominal regions (for the peripheral abdomen, 6.07 ± 2.98 × 10−3 v 0.40 ± 0.72 × 10−3 × min−1, P < .005), but not in the hindlimb. In sepsis, the albumin leak index increased more in the abdomen than in the lungs (P < .05). We conclude that in porcine septic shock pulmonary microvascular permeability is increased, but the microvascular albumin flux and thus plasma extravasation increased more in the abdomen than in the lungs.

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Ben J. Appelmelk

VU University Medical Center

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F.A.N. Zoetmulder

Netherlands Cancer Institute

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