Search PubMed⌕ Search

Biomedical subjects

M Frass

Publications and source records attributed to M Frass.

At least 55 records · Page 3Linked to original sources
PubMed1999

Continuous infusion versus intermittent administration of meropenem in critically ill patients.

This prospective crossover study compared the pharmacokinetics of meropenem by continuous infusion and by intermittent administration in critically ill patients. Fifteen patients were randomized to receive meropenem either as a 2 g iv loading dose, followed by a 3 g continuous infusion (CI) over 24 h, or by intermittent administration (IA) of 2 g iv every 8 h (q8h). Each regimen was followed for a period of 2 days, succeeded by crossover to the alternative regimen for the same period. Pharmacokinetic parameters (mean +/- SD) of CI included the following: concentration at steady state (Css) was 11.9+/-5.0 mg/L; area under the curve (AUC) was 117.5+/-12.9 mg/L x h. The maximum and minimum serum concentrations of meropenem (Cmax, Cmin) and total meropenem clearance (CItot) for IA were 110.1+/-6.9 mg/L, 8.5+/-1.0 mg/L and 9.4+/-1.2 L/h, respectively. The AUC during the IA regimen was larger than the AUC during CI (P < 0.001). In both treatment groups, meropenem serum concentrations remained above the MICs for the most common bacterial pathogens. We conclude that CI of meropenem is equivalent to the IA regimen and is therefore suitable for treating critically ill patients. Further studies are necessary to compare the clinical effects of CI and IA in this patient group.

Adolescent↗
PubMed1999

Amoxycillin/clavulanic acid combinations increase transmigration of leucocytes through endothelial cell monolayers: endothelial cells play a key role.

Postoperative inflammation is still viewed as an unresolved problem. During inflammation, leucocytes play a tremendous role and migrate from intravascular spaces into the tissue to attack microorganisms. Different agents, e.g. anaesthetic drugs, are able to influence leucocyte recruitment. Previous studies have investigated the influence of amoxycillin on chemotaxis of leucocytes alone. The aim of our study was to examine the effect of amoxycillin/clavulanic acid (co-amoxiclav) on leucocyte migration through endothelial cell monolayers (ECMs). Human umbilical endothelial cells were cultured on microporous membranes, achieving a monolayer. Polymorphonuclear neutrophil leucocytes (PMNLs) were used in a migration assay. The numbers of untreated PMNLs migrating through untreated ECMs were used as control and set as 100%. PMNLs and/or ECMs were pretreated with co-amoxiclav using clinically relevant as well as higher and lower concentrations. Co-amoxiclav was able to increase PMNL migration through ECMs significantly (P<0.05) when both cell types were treated (291+/-18.7%). When PMNLs or ECMs were treated alone, it could be shown that ECMs were more affected than PMNLs. The greatest effect was shown when both cell types, PMNLs and ECMs, were treated. In conclusion, co-amoxiclav was identified as a potent drug to increase leucocyte transmigration through ECMs. ECMs were also critically involved. Co-amoxiclav also affects endothelial cells.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1999

The assessment of four different methods to verify tracheal tube placement in the critical care setting.

UNLABELLED: One of the most serious complications of conventional endotracheal intubation is unidentified placement of the tube in the esophagus. The aim of our study was to evaluate four different methods for immediate detection of the tube position: auscultation, capnographic determination of ETCO2, esophageal detection method (EDM) using a self-inflating bulb, and the transillumination method using a lighted stylet (Trachlight; Laerdal, Armonk, NY). Thirty-eight endotracheally intubated patients admitted to our medical intensive care unit were enrolled in the study. A second identical tube was inserted into the esophagus under laryngoscopic control. The endotracheal tube was then disconnected from the ventilator. Two blinded examiners, one experienced, the other inexperienced, determined the tube position within 30 s using one of the four methods. The order of the tubes tested and the methods used were randomized. In 130 of 152 examinations, both examiners correctly diagnosed the position of the tube. The wrong result was obtained by both examiners 4 times; only the experienced examiner was wrong 4 times, and only the inexperienced examiner was wrong 14 times. Using ETCO2, both examiners were correct in all cases. Auscultation showed an obvious relation to the examiner's experience: the experienced examiner was correct in all cases, the inexperienced examiner was correct in only 68% of cases. Using the self-inflating bulb, there were two wrong results of the experienced examiner and one wrong result of the inexperienced examiner. The transillumination technique was associated with a high error rate by both examiners (16% and 13%, respectively). Comparing all four methods showed that capnography is superior to auscultation (P = 0.0005) and to the Trachlight detection method (P = 0.0078). EDM was not statistically superior to auscultation and transillumination. Capnography was the most reliable method for rapid evaluation of tube position, followed by EDM, whereas auscultation and Trachlight did not seem to be of comparable value. Experience was a determining factor for auscultation. IMPLICATIONS: To prevent unidentified esophageal intubation, a serious complication in the critical care setting, four methods for detecting tube position were tested by two examiners (one experienced, the other inexperienced) in endotracheally intubated patients after insertion of a second tube into the esophagus.

Adult↗
PubMed1999

Propofol reduces the migration of human leukocytes through endothelial cell monolayers.

OBJECTIVE: To test propofol and the solvent of propofol on leukocyte function in the presence of endothelial cell monolayers. The interactions of leukocytes with endothelial cells play a tremendous role during inflammation. Previous studies have investigated the influence of propofol on leukocytes. DESIGN: Prospective, controlled study. SETTING: University research laboratories. SUBJECTS: Seven independent experiments were performed to investigate the influence of propofol (0.4, 4, and 40 ng/mL) on the migration of human leukocytes through human endothelial cell monolayers. Moreover, the authors tested the solvent of propofol on leukocyte migration. INTERVENTIONS: Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant higher and lower concentrations of propofol. The amount of leukocyte migration after 3 hrs was measured with a fluorometer. MEASUREMENTS AND MAIN RESULTS: Human endothelial cells isolated from umbilical veins were cultured on microporous membranes until they formed an endothelial cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells using the clinically relevant concentration of propofol was reduced to 93% +- 3.8% (so; p < .05) when the leukocytes but not the endothelial cell monolayers were preincubated with propofol. Leukocyte migration was reduced to 80% - 5.9% (p < .05) when only monolayers of endothelial cells were treated with propofol, and was reduced to 73% + 10.4% (p < .05) when both leukocytes and monolayers of endothelial cells were treated with propofol. The higher and lower concentrations showed a dose-dependent effect. The solvent of propofol had no significant effect. CONCLUSION: The authors investigated the influence of propofol and its solvent on the interaction between both cell systems-leukocytes and endothelial cells. Propofol is able to reduce significantly the migration of leukocytes through endothelial cell monolayers. The use of different doses revealed a dose-dependent effect. The current model allowed treatment of one cell type: leukocyte or endothelial cell. The results of this investigation indicate that the influence of propofol on leukocyte migration affects endothelial cells more than leukocytes.

Anesthetics, Intravenous↗
PubMed1999

Meloxicam effect on leukocyte migration under shear stress: a new perfused triple chamber (Hofbauer chamber) assay simulating an in vitro vascular wall.

BACKGROUND: Leukocyte migration plays a tremendous role during inflammation. Different drugs are able to influence migration of leukocytes. Several authors have attempted to establish methods for investigation of leukocyte migration. Migration of leukocytes under conditions simulating natural blood flow and shear stress is poorly understood. Moreover, leukocyte migration in the simultaneous presence of endothelial cells and smooth muscle cells (SMC) has not yet been examined thoroughly. The aim of the current study was to create a new three-dimensional assay investigating migration during simulated perfusion. The assay was used for investigating the effect of meloxicam on leukocyte migration under shear stress. METHODS: Different concentrations of meloxicam (0.09, 0.9, and 9.0 ng/mL) were used in a newly developed triple migration chamber system for investigation of leukocyte migration (n = 7). This new system allows inclusion of SMC-layers. Assay precision tests were done using intra-assay (within-day variability) and interassay (day-to-day variability) controls. RESULTS: Intra-assay and interassay controls showed reliable results (coefficient of variation: intra-assay 8.53%; interassay 11.39%). Meloxicam in a clinically relevant concentration of 0.9 ng/mL was able to reduce the migration of leukocytes under shear stress (71 +/- 14% SD; P < 0.05), whereas higher and lower concentrations showed a dose dependent effect. CONCLUSION: This new perfusion system allows investigation of drugs, such as meloxicam, on leukocyte migration under shear stress. Moreover, this assay may be used for studies on other cell-cell interactions, as well as on drug influences.

Adult↗
PubMed1999

Negative chronotropic effects of fentanyl attenuate beneficial effects of dobutamine on oxygen metabolism: hemodynamic and pharmacokinetic interactions.

Opioids are well known to cause cardiovascular depression. The aim of the present investigation was to determine whether an interaction of opioid derivatives with catecholamines might be involved in these hemodynamic alterations. Six comatose patients were enrolled into a prospective, nonrandomized pilot trial. All patients first received a continuous i.v. infusion of dobutamine (10 microgram. kg-1. min-1) paralleled by continuous administration of midazolam (0.4 mg. kg-1. h-1); thereafter, fentanyl was added i.v. (4 microgram. kg-1. h-1). Hemodynamic parameters as well as dobutamine and endogenous catecholamines plasma levels were determined. The mean arterial blood pressure did not change significantly during the whole study period. The continuous administration of dobutamine (steady-state plasma concentrations: 217 +/- 118 ng. ml-1) increased the beta1-adrenergic receptor-mediated hemodynamic parameters such as heart rate, stroke volume index, cardiac index, and oxygen delivery index (p <.05). The concomitant administration of fentanyl decreased the heart rate-dependent hemodynamic parameters (p <.05), suggesting that fentanyl antagonizes the chronotropic effects of dobutamine. In parallel, dobutamine plasma levels increased significantly (275 +/- 165 ng. ml-1; p <.05). Noteworthy, after administration of fentanyl, oxygen delivery and consumption index returned to baseline values. Radioligand binding experiments on rat cardiac ventricular microsomes ruled out a direct interaction of fentanyl with beta-adrenergic receptors and, more importantly, a fentanyl-induced inhibition of beta-adrenergic receptor G protein coupling. Our observations suggest that fentanyl inhibits the frequency-related hemodynamic changes induced by dobutamine. The underlying mechanism is independent of beta-adrenergic receptors, but is powerful enough to abolish the salutary effect of dobutamine on oxygen delivery and consumption.

Aged↗
PubMed1999

The immune system and the effects of non-volatile anesthetics on neutrophil transmigration through endothelial cell monolayers.

Inflammation represents the consequence of capillary dilation with accumulation of fluid and transmigration of leukocytes into the surrounding tissue. Leukocytes play a major role in the defense system of the body against invading microorganisms. This defense system has a non-specific branch consisting of granulocytes and macrophages and a specific branch of lymphocytes. Granulocytes release cytotoxic compounds from their intracellular granules into their local environment when encountering microorganisms. This random destruction happens rapidly, but it may also harm healthy tissue of the body. Leukocytes patrol the body by circulating through the blood and lymphatic system ensuring a continuous surveillance which is a prerequisite for an efficient defense. Upon tissue damage and inflammation, leukocytes are recruited from the blood to sites of injury, and this trafficking displays exquisite specificity. In the late 1890 s, Metchnikoff noted the power of certain blood cells to move towards microorganisms and ingest them. In fact, leukocytes adhere to the endothelium of the blood vessels, and subsequently leave the circulation by transmigration through the intercellular junctions of the endothelial cell monolayer. Transmigration is driven by chemoattractants, a process known as diapedesis. Reversible adherence of leukocytes to the endothelium, basement membranes, and other surfaces is an essential event in the establishment of inflammation, whose molecular basis is beginning to be understood. Inflammation may become chronic in many pathophysiologic processes and disease states. In long-term mechanically ventilated critically ill patients, non-volatile anesthetics are needed over a prolonged time period. Perioperative infections are a major cause of morbidity and mortality in critically ill patients. Therefore, the influence of non-volatile anesthetics and opioid agents on the immune system is of high interest. After presentation of the different effectors of the immune system and their fluxes through the body, the aim of this review is to propose a general model of leukocyte transmigration through endothelial cell monolayers. It emphasizes in which way different non-volatile anesthetic drugs may affect the non-specific branch of the immune system, i.e. the leukocyte transmigration through endothelial cell monolayers.

Anesthetics↗
PubMed1998

Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis.

The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.

Adult↗
PubMed1998

Thiopental inhibits migration of human leukocytes through human endothelial cell monolayers in vitro.

OBJECTIVES: The interactions between blood and vascular wall cells are essential for the understanding of pathophysiologic processes, e.g. inflammation. The influence of the anesthetic drug thiopental on leukocyte function is well documented. Recently, an inhibitory effect of thiopental on leukocyte chemotaxis in a Boyden chamber assay (i.e. endothelial cells were not included) was demonstrated. In vivo, leukocytes have to interact with endothelial cell monolayers to invade the tissue. The influence of thiopental on a monolayer of endothelial cells has not yet been investigated. The aim of the current study was to investigate the influence of thiopental on the migration of leukocytes through endothelial cell monolayers (ECM). MATERIAL AND METHODS: Human umbilical vein endothelial cells (HUVEC) were isolated and cultured on microporous membrane filters to achieve a monolayer. Isolated polymorphonuclear leukocytes (PMNL) as well as ECM were preincubated with different concentrations of thiopental. The rate of leukocyte migration against the chemotactic protein formyl-methyl-leucyl-phenylalanine was measured (n = 7). Thiopental was able to reduce the amount of leukocyte migration through ECM significantly. CONCLUSION: In conclusion, we could show that thiopental is able to reduce the migration of PMNL through ECM significantly.

Adult↗
PubMed1998

Leukocyte migration: a new triple migration chamber assay allows investigation of various cell interactions simultaneously.

Examination of the interactions between various cells of the vascular wall and blood components are essential for understanding different pathophysiological processes. Such investigations require appropriate techniques. Several groups have attempted to establish different methods. In all blood vessels except capillaries, endothelial cells (EC) and smooth muscle cells (SMC) coexist and interact very closely. The current study describes a new 3-dimensional triple chamber migration assay, studying leukocyte migration through human endothelial cell monolayers (ECM) towards human SMC layers simultaneously. To test the new assay, SMC-layers were prestimulated with different concentrations of tumor necrosis factor alpha (TNF-alpha, 1 ng/ml, 10 ng/ml, 100 ng/ml) over 6 hours. Then, two microporous membranes, a collecting membrane and a third membrane with cultured ECM, were inserted. Freshly isolated peripheral blood mononuclear cells (PBMNC) were seeded on the ECM and transmigrated cells were measured after further 3 hours incubation. The migration against non stimulated SMC-layers was used as control. Prestimulated SMC-layers led to a dose dependent increase of PBMNC migration into the subendothelial cell space. Antibodies against interleukin-1 reduced the PBMNC migration. In conclusion, this assay allows to study cell migration into the subendothelial space and interactions between different vascular cells. Moreover, this assay can also be used for studies on other cell-cell interactions in man.

Cell Migration Inhibition↗
PubMed1998

Time course of immunological markers in patients with the systemic inflammatory response syndrome: evaluation of sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and TGF-beta 2.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) is viewed as a system-wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cells adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta 2 (TGF-beta 2) as early markers of outcome in patients with SIRS. METHODS: A group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: At the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM-1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non-survivors, with the exception of interleukin (IL) 6 at day 7. CONCLUSION: All evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.

Adult↗
PubMed1998

Sufentanil inhibits migration of human leukocytes through human endothelial cell monolayers.

UNLABELLED: The interactions between blood and vascular wall cells are essential for understanding pathophysiological processes, e.g., during inflammation. The influence of anesthetics on leukocyte function is well documented. An inhibitory effect of thiopental, midazolam, and ketamine on leukocyte chemotaxis in a Boyden chamber chemotaxis assay (i.e., endothelial cells were not included) has been demonstrated. Little is known, however, about the influence of sufentanil on the inflammatory processes. To reach their targets in the tissue in vivo, leukocytes must interact with endothelial cell monolayers (ECMs). The aim of the current study was to investigate the influence of sufentanil on the migration of leukocytes through an ECM. Human umbilical vein endothelial cells were cultured to achieve a monolayer. Isolated polymorphonuclear leukocytes and ECM were preincubated with different concentrations of sufentanil. The rate of leukocyte migration against the chemotactic protein formyl-methyl-leucyl-phenylalanine was measured (n = 7). Sufentanil significantly reduced the amount of leukocyte migration through ECM to 77%+/-7.8% (P < 0.05 compared with control). Endothelial cells as well as leukocytes contributed to this effect: treatment of both cell types showed an additive effect. Although lower concentrations showed no effect, high concentrations reduced leukocyte migration through ECM to 61%+/-7.1%. IMPLICATIONS: Leukocytes play an important role during inflammation, and anesthetics influence leukocyte functions, e.g., respiratory burst or chemotaxis. The effect of sufentanil on transendothelial leukocyte migration has not been investigated. Therefore, we used a migration assay including endothelial cell monolayers. Sufentanil showed a reducing effect on transendothelial leukocyte migration.

Adult↗
PubMed1998

Comparison of oxygen cost of breathing with pressure-support ventilation and biphasic intermittent positive airway pressure ventilation.

OBJECTIVE: To assess the oxygen cost of breathing with either pressure-support ventilation (PSV) or biphasic intermittent positive airway pressure ventilation (BIPAP). DESIGN: Prospective, randomized, crossover study. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Twenty clinically stable and spontaneously breathing patients after long-term mechanical ventilation. INTERVENTIONS: Patients were randomized to start on either PSV or BIPAP, and measurements were performed after an adaptation period of 30 mins. Immediately after, the ventilatory mode was changed and after another 30-min adaptation period, the same measurements were performed. MEASUREMENTS AND MAIN RESULTS: Indirect calorimetry was performed during each ventilatory mode for a period of 30 mins. Oxygen consumption, energy expenditure, CO2 production, and respiratory quotient did not differ significantly between the two ventilatory modes, regardless of the patients' randomization. There were no statistically significant differences with regard to respiratory rate, minute volume, and blood gas analysis. All patients tolerated both ventilatory modes without any signs of discomfort. CONCLUSIONS: Pressure support ventilation and BIPAP are both used for weaning patients gradually from the ventilator. BIPAP may be advantageous in patients not breathing sufficiently with PSV, since no patient effort is necessary with use of this ventilatory mode.

Adult↗
PubMed1998

Ketamine significantly reduces the migration of leukocytes through endothelial cell monolayers.

OBJECTIVE: To study the role of neutrophils in host defense, using human endothelial cells in migration studies in the presence of ketamine (0.3, 3, and 30 microg/mL). DESIGN: Prospective, controlled study. SETTING: University research laboratories. SUBJECTS: Seven independent experiments from different donors were done, investigating the influence of ketamine (0.3, 3, and 30 microg/mL) to the migration of human leukocytes through human endothelial cell monolayers. INTERVENTIONS: Human endothelial cell monolayers and/or human leukocytes were preincubated with clinically relevant (3 microg/mL), higher (30 microg/mL), and lower (0.3 microg/mL) concentrations of ketamine. The amount of leukocyte migration after 3 hrs was measured in a fluorometer. MEASUREMENTS AND MAIN RESULTS: Human endothelial cells isolated from umbilical veins were cultured on microporous membranes (polyethylene-terephthalat membranes) until they formed an endothelial cell monolayer. Leukocytes were separated by standard procedures. The migration of leukocytes through monolayers of endothelial cells under the clinically relevant concentration of ketamine was reduced to 59+/-9.8% (SD) (p< .05) when leukocytes but not the endothelial cell monolayers were preincubated with ketamine. Leukocyte migration was reduced to 92+/-7.3% (p > .05) when only monolayers of endothelial cells were treated with ketamine, and to 52+/-8.8% (p< .05) when both leukocytes and monolayers of endothelial cells were treated with ketamine. The higher and lower concentrations showed a dose-dependent effect. CONCLUSIONS: We investigated the cellular interaction between both cell systems, leukocytes and endothelial cells, simultaneously in the presence of ketamine. Ketamine is able to reduce significantly the migration of leukocytes through endothelial cell monolayers. The use of different dosages revealed a dose-dependent effect. The current model allowed treatment of one cell type, either leukocyte or endothelial cell. Ketamine inhibits the function of leukocytes more than the function of endothelial cells.

Anesthetics, Dissociative↗