Search PubMed⌕ Search

Biomedical subjects

G Marx

Publications and source records attributed to G Marx.

At least 19 recordsLinked to original sources
PubMed2006

The critical role of aprotinin in controlling haemostasis in conjunction with non-pharmacological blood-saving strategies during routine coronary artery bypass surgery.

OBJECTIVE: Aprotinin, a non-specific serine protease inhibitor, has been confirmed to be safe and effective in reducing intra- and postoperative blood drainage, transfusion requirements, and perioperative morbidity and mortality during coronary artery bypass surgery. It is the only one of the currently available haemo-static agents that is approved by the U.S. Food and Drug Administration (FDA) for use in cardiac surgery. However, one major weakness of currently available trials is the lack of information regarding the concomitant usage of aprotinin with blood-saving strategies that have been used more frequently in recent years. METHODS: Patients undergoing elective first-time coronary artery bypass grafting (n = 172) who were given systemic high-dose aprotinin (n = 85), combined systemic high-dose aprotinin and topical aprotinin (n = 27), or no aprotinin (n = 60) were reviewed retrospectively. The use of all blood-saving procedures was systematically taken in account. RESULTS: Postoperative blood drainage was significantly less in patients treated with aprotinin than controls (P < 0.0001). Concomitant use of topical aprotinin was accompanied by a postoperative blood loss reduction of 35% compared to systemic aprotinin use alone (P < 0.003). The intra- and postoperative donor blood requirements were dramatically reduced in both aprotinin-treated groups compared to controls, although patients received different blood saving strategies as appropriate (P < 0.0001). A trend of up to 20% lower postoperative blood drainage was noted in patients in whom intraoperative haemodilution and autologuos blood transfusions were used (P > 0.05). CONCLUSIONS: The present analysis demonstrates that the local and systemic administration of aprotinin is safe and effective in reducing intra- and postoperative blood drainage and transfusion requirements. In elective CABG procedures, aprotinin should still be used even if blood-saving strategies are employed.

Adult↗
PubMed2006

Haemodynamic, acid-base and blood volume changes during prolonged low pressure pneumoperitoneum in rabbits.

BACKGROUND: The anaesthetic management of small infants during advanced laparoscopic surgery can be complicated by the major pathophysiological effects of increased intra-abdominal pressure. In this study haemodynamic, acid-base and blood volume changes were investigated during pneumoperitoneum in a small animal model. METHODS: Ten fasted, anaesthetized, mechanically ventilated and multi-catheterized New Zealand rabbits were randomized to carbon dioxide pneumoperitoneum (PP, duration 210 min, pressure 8 mm Hg) or control group. Cardiac index was determined using trans-cardiopulmonary thermodilution and total blood volume was measured by thermal-dye dilution with indocyanine green using a fibreoptic monitor system. RESULTS: In PP cardiac index (CI), central venous oxygen saturation (Scv(O(2))), total blood volume (TBV) and base excess (BE) decreased significantly during the study whereas all variables remained constant in the control group. After release of PP the measured variables did not return to baseline within 30 min [PP, baseline vs study end: CI 108 (22) vs 85 (14) ml kg(-1) min(-1), Scv(O(2)) 81.4 (8.9) vs 56.7 (9.8)%, TBV 318 (69) vs 181 (54) ml, BE -1.9 (2.7) vs -8.7 (1.8) mmol litre(-1); P<0.01]. CONCLUSION: Our animal model suggests that a decrease in CI, metabolic acidosis and hypovolaemia could occur after prolonged low pressure pneumoperitoneum in small infants, which is possibly not detectable by the standard monitor setting. Therefore, the routine use of an extended monitoring including measurement of central venous oxygen saturation and acid-base parameters should be considered during and soon after operation, when pneumoperitoneum will last longer than 2 h.

Acidosis↗
PubMed2006

Isolation of mesenchymal stem cells from G-CSF-mobilized human peripheral blood using fibrin microbeads.

Adult mesenchymal stem cells (MSC) that are able to differentiate into various mesenchymal cell types are typically isolated from bone marrow, but their significant presence in human peripheral blood (PB) is controversial. Fibrin microbeads (FMB) that bind matrix-dependent cells were used to isolate MSC from the mononuclear fraction of mobilized PB of adult healthy human donors treated with a granulocyte colony-stimulating factor. Isolation by plastic adherence resulted in a negligible number of MSC in all samples tested, whereas FMB-based isolation yielded spindle-shaped cell samples that could further expand on plastic or on FMB in eight out of the 11 samples. The yield of these cells at days 17-18 after the harvest was approximately 0.5% of the initial cell number. The isolated cells were grown on plastic and characterized by FACS analysis and immunohistochemistry for specific markers. Following culturing and first passage, the FMB-isolated cells stained positive for mesenchymal stromal cell markers CD90 and CD105, expressed vimentin and fibronectin and were negative for hematopoietic markers CD45 and CD34. These cells could differentiate into osteoblasts, adipocytes and chondrocytes. This study indicates that FMB may have special advantage in isolating MSC from sources such as mobilized PB, where the number of such cells is scarce.

Antigens, CD↗
PubMed2006

Fibrin microbeads (FMB) as a 3D platform for kidney gene and cell therapy.

Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.

Cell Differentiation↗
PubMed2006

Reliability of continuous cardiac output determination by pulse-contour analysis in porcine septic shock.

BACKGROUND: Pulse-contour analysis represents a technique for cardiac output (CO)-measurement and allows continuously monitoring trends in CO. We evaluated reliability of pulse-contour CO (COpc) in septic shock. METHODS: Seventeen anaesthetized and mechanically ventilated pigs were investigated. After baseline measurements, 14 animals received 0.75 g/kg body weight faeces into the abdominal cavity to induce sepsis and were observed over 9 h, three animals served as controls. A central venous catheter was inserted into the jugular vein and an arterial catheter for thermodilution was inserted into the femoral artery. Two bedside computers were used for COpc. After induction of sepsis, COpc-computer No. 1 (COpcCAL) was recalibrated hourly. No further calibrations were performed in computer No. 2 (COpcNoCAL). We directly compared COpcCAL hourly before recalibration with COpcNoCAL. One hundred and seventy parallel triplicate determinations of CO were analysed using the method of Bland-Altman. RESULTS: Three hours after sepsis induction, correlation between recalibrated and non-recalibrated CO was r = 0.74, P < 0.01, at 5 h r = 0.59, P < 0.05 and 9 h r = 0.02, NS. Three hours after sepsis induction, bias +/- SD (limits of agreement) between both groups was 1.6 +/- 15.5 (-29.4-32.6) ml/kg/min, at 5 h -15.0 +/- 24.3 (-63.6-33.7) ml/kg/min and at 9 h -87.0 +/- 90.8 (-268.5-94.6) ml/kg/min. CONCLUSION: Continuous CO determination using pulse-contour analysis is a reliable method of assessing CO up to 5 h without recalibration in porcine septic shock. Thus, COpc may be a useful tool for assessment of unpredictable haemodynamic changes in sepsis.

Animals↗
PubMed2005

[New approaches to intensive care for sepsis].

In Germany, the mortality from sepsis remains high, and up to 60,000 patients die from it each year. Thus, sepsis is the third most common cause of death. More deaths occur only from coronary heart disease and acute myocardial infarction. In the last 3-4 years, substantial progress in sepsis therapy has been made. Based on these achievements, there is hope of reducing sepsis mortality by 25% in the next few years. Implementing new medical evidence in this context into daily clinical intensive care remains a major hurdle. The early diagnosis of sepsis prior to the onset of clinical deterioration is of particular interest, because this would increase the possibility of early and specified treatment, which is in turn the major determining factor of mortality in septic patients.

Cause of Death↗
PubMed2005

Comparison of cardiac output measurements by arterial trans-cardiopulmonary and pulmonary arterial thermodilution with direct Fick in septic shock.

BACKGROUND AND OBJECTIVE: The aim of this study was to compare cardiac output (CO) measurements by arterial trans-cardiopulmonary thermodilution (ATD) and pulmonary arterial thermodilution (PATD) with CO estimated on the basis of the Fick calculation via a metabolic monitor in septic shock. METHODS: In a prospective animal study 20 anaesthetized, ventilated pigs (20.9 +/- 1.9 kg) were investigated. Septic shock was induced with faecal peritonitis. A pulmonary artery catheter was used for conventional measurement of CO. Simultaneously ATD was measured with a thermistor tipped catheter inserted into right carotid artery. Whole body oxygen consumption was measured by indirect calorimetry. Eighty data pairs of simultaneous CO measurements were analysed. RESULTS: CO measured with Fick and that measured with PATD were significantly correlated (r = 0.94, r = 0.87, P < 0.001). Mean CO measured by PATD was 94.3 +/- 40.1 mL min(-1) kg(-1). Bias was 10.1 mL min(-1) kg(-1) (95% confidence interval (CI): 6.0-14.2 mL min(-1) kg(-1)) with limits of agreement of -26.8 to 47.0 mL min(-1) kg(-1). Correlation between Fick derived CO estimation and ATD CO was similar (r = 0.91, r2 = 0.83, P < 0.001). Mean CO measured by trans-cardiopulmonary thermodilution was 104.3 +/- 43.2 mL min(-1) kg(-1). Bias was 0.75 mL min(-1) kg(-1) (95% CI: -3.8 to 5.3 mL min(-1) kg(-1)) with limits of agreement of -39.7 to 41.2 mL min(-1) kg(-1). CONCLUSIONS: Even during haemodynamic instability in septic shock the correlation of arterial trans-cardiopulmonary thermodilution and PATD derived CO with direct Fick was good. As arterial trans-cardiopulmonary thermodilution is less invasive than PATD, the former may offer practical advantages.

Algorithms↗
PubMed2005

Terminal complement complex in septic shock with capillary leakage: marker of complement activation?

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the value of terminal complement complex (C5b-9) plasma levels as a marker for complement activation in septic shock with concomitant capillary leak syndrome. METHODS: In a prospective animal study 10 fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.6 +/- 1.3 kg) were investigated over a period of 8 h. Sepsis was induced by faecal peritonitis (1 g kg(-1) body weight faeces, n = 5) and compared to controls (n = 5). The animals received 6% hydroxyethyl starch 200/0.5 to maintain a central venous pressure of 12 mmHg. To quantify capillary leak syndrome, albumin escape rate was measured using 99mTc-labelled human serum albumin. Plasma levels of terminal complement complex were measured in a double antibody immunoassay (neoepitope-specific MoAb aE 11 as catching antibody). Immunohistological studies of renal specimens were performed to detect terminal complement complex deposition. RESULTS: Albumen escape rate increased in septic animals (+ 52%) compared to controls (+ 3%, P < 0.05). Plasma levels of terminal complement complex decreased during the study period in both groups. In septic animals this finding was accompanied by a significant deposition of terminal complement complex in renal specimens (P < 0.05). CONCLUSION: We found an activation of the complement system proven by marked deposition of terminal complement complex in renal specimen, while its plasma levels decreased during the study period in septic and control animals. These results suggest that in septic shock with capillary leak syndrome plasma level of terminal complement complex may not be a reliable marker of complement activation.

Animals↗
PubMed2005

Fusobacterium necrophorum-induced sepsis: an unusual case of Lemierre's syndrome.

Classical Lemierre's syndrome is characterized by severe sepsis with metastatic abscess formation in young, previously fit people from a primary head or neck focus. The causative organisms are the anaerobic fusobacteria, most commonly Fusobacterium necrophorum. We describe the evaluation, therapeutic interventions and management of a patient with Lemierre's syndrome who presented in septic shock with multiple organ dysfunction. The patient required immediate interventions including endotracheal intubation and mechanical ventilation, fluid resuscitation, inotropic support, bilateral thoracostomy tube drainage of empyemata and antimicrobial therapy. The unexpected isolation of Fusobacterium necrophorum from blood cultures and empyema fluid necessitated a change of antibiotic regime to provide anaerobic cover. The patient required 4 weeks of intensive support including prolonged antimicrobial therapy, and after a further 2 weeks was discharged home from hospital. This case highlights the need to raise the awareness of 'the forgotten disease': Lemierre's syndrome. Its diagnosis may, as in this case, be confounded by a lack of symptoms of pharyngitis at the time of presentation, and end-organ dysfunction associated with severe sepsis, possibly suggesting an alternative source of infection. As appropriate antibiotics reduce mortality dramatically, clinicians need to be alert to Lemierre's syndrome and include it in the differential diagnosis in young but otherwise healthy patients presenting with severe sepsis.

Adult↗
PubMed2005

Outpatient treatment with subcutaneous interleukin-2, interferon alpha and fluorouracil in patients with metastatic renal cancer: an Australian experience.

BACKGROUND: Metastatic renal cell cancer has a poor prognosis and survival. Conventional cytotoxic chemotherapy has no impact on survival and response rates are low. Biologic agents are the most active in treating this disease. We report the feasibility of administering a combination of interferon alpha, subcutaneous interleukin-2 and 5Fluorouracil in the outpatient setting to patients with metastatic renal cell cancer. RESULTS: Between September 1996 and August 2003, fourteen patients were treated with this combination: ten males and four females with a median age of 50 (42-66). Thirteen patients had Eastern Cooperative Oncology Group performance scores of 0 or 1. Ten patients had had nephrectomies. Six patients had undergone prior treatments with chemotherapy or hormonal therapy. Twenty-two cycles were administered (median 1, range of 1-4). Three patients achieved partial response, eight patients had stable disease, and three had progressive disease. The duration of response in patients with stable disease was (3, 3+, 4, 4+, 5+, 6, 10, 11 months) and for the patients with a partial response was 2+, 11 and 12 months. Toxicities with this combination were predictable. There were no treatment-related deaths and no episodes of febrile neutropenia. One patient ceased treatment as a result of toxicity. Fatigue was the most common side-effect. Myalgias, fever and rigors occurred within 6-12 h of administration of interleukin-2, and resolved within 12 h. Grade 1-2 nausea and vomiting occurred in most patients. Four patients had transient asymptomatic transaminitis, which resolved spontaneously. As a result of toxicity, one patient had treatment ceased in his 6th week. CONCLUSION: This combination was feasible, well tolerated and manageable in an outpatient setting.

Administration, Cutaneous↗
PubMed2004

Ringer's solution but not hydroxyethyl starch or modified fluid gelatin enhances platelet microvesicle formation in a porcine model of septic shock.

BACKGROUND: Sepsis is associated with volume deficit and clotting system activation. Platelet activation in sepsis results in an increased formation of microvesicles, which in turn, have been associated with increased mortality. We hypothesized an effect of different volume replacement solutions on platelet-derived microvesicle formation in septic shock. METHODS: Anaesthetized, mechanically ventilated and multi-catheterized pigs received 1 g kg(-1) body weight faeces into the abdominal cavity to induce sepsis and were observed over 8 h. Five animals in each group received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% hydroxyethylstarch (HES) 200/0.5 or Ringer's solution (RS) to maintain a central venous pressure of 12 mm Hg. Flow cytometry was used for determination of microvesicles before induction of sepsis (baseline) and after 8 h. Platelets and microvesicles were identified with an anti-platelet monoclonal Ab and a secondary antibody. Microvesicles were determined as the smallest 1-3% positive cells in forward scatter. Intergroup comparisons were performed using Wilks-Lambda and Ryan-Einot-Gabriel-Welsh F-test. Differences within groups were compared using a two-tailed Student's t-test. RESULTS: Baseline values were considered as 100%. While microvesicle formation was reduced in HES (73 (sd 19)%), MFG4% (63 (41)%) and MFG8% groups (53 (17)%), an increase in the RS-group (210 (121)%) was observed. Eight hours after induction of sepsis, formation of microvesicles was significantly higher in the RS group compared to all colloid-treated groups. CONCLUSION: In this porcine septic shock model the formation of platelet-derived microvesicles was significantly increased by volume replacement with Ringer's solution in comparison to colloid solutions.

Animals↗
PubMed2004

Surface acoustic waves for the characterization of BN-coated fibres observed by Brillouin light scattering.

The observation of acoustic phonons located at the surface of uncoated fibres or guided in thin films deposited on fibres by Brillouin light scattering spectroscopy (BLS) is reported. The BLS technique is non-destructive and non-intrusive and is well applicable to non-planar sample geometries. Investigations were carried out on bundles of commercially available carbon fibres, in which a single fibre was 5 microm in diameter. With regard to the detected surface acoustic excitations, each fibre can be considered as an infinite halfspace owing to the large ratio of fibre diameter to wavelength. The shear modulus, which is highly relevant for the intended technical application, was determined by measurement of the Rayleigh mode phase velocity of the uncoated fibres. These fibre bundles were coated with boron nitride (BN) in a continuously driven thermal chemical vapour deposition (CVD) process using trimethyl borate and ammonia as precursors. In comparison to carbon, BN is expected to improve the mechanical properties of fibre-reinforced composites such as fracture toughness at high temperatures. The measured velocity dispersion of the Rayleigh mode of this film-on-substrate system permitted the comparison of the shear stiffness of the carbon fibre and of the BN film material. The results evidence the desired effect of a distinct stiffness reduction of the coated fibre relative to the uncoated fibre in the near-surface region. Additional information can be obtained on the homogeneity of the deposition across the whole fibre bundle.

Journal Article↗
PubMed2004

Assessing fluid responsiveness by stroke volume variation in mechanically ventilated patients with severe sepsis.

BACKGROUND AND OBJECTIVE: Our hypothesis was that stroke volume variation during mechanical ventilation of the lungs would allow accurate prediction and monitoring of changes in cardiac index in response to fluid loading in patients with severe sepsis. METHODS: This was a prospective clinical study in a university hospital. Ten mechanically ventilated patients with severe sepsis or septic shock were given fluid loading with 500 mL 10% hydroxyethylstarch 200/0.5 over 30 min. Before and after fluid loading pulmonary arterial occlusion pressure and central venous pressure were measured. Intrathoracic blood volume index, stroke volume variation and cardiac index were measured by the transpulmonary thermodilution technique. After verifying normal distribution of the data (skewness < 1.0) the paired t-test was used for statistical analysis. RESULTS: After fluid loading stroke volume variation decreased significantly, whereas central venous pressure, pulmonary arterial occlusion pressure, intrathoracic blood volume index and cardiac index increased significantly. Changes of cardiac index in response to fluid loading were correlated to baseline values of stroke volume variation (r = 0.64, P = 0.02) and intrathoracic blood volume index (r = -0.73, P = 0.009). Changes in cardiac index were significantly correlated to percentage changes in stroke volume variation (r = -0.65, P < 0.001) and changes in intrathoracic blood volume index (r = 0.52, P = 0.002), whereas changes in cardiac index revealed no significant correlation to changes in central venous pressure (r = 0.28, P = 0.07) and changes in pulmonary arterial occlusion pressure (r = 0.29, P = 0.06). CONCLUSIONS: Measuring stroke volume variation may be a useful way of guiding fluid therapy in ventilated patients with severe sepsis because it allows estimation of preload and prediction of cardiac index changes in response to fluid loading.

Adult↗
PubMed2003

Comparative investigations of structure and properties of BCN coatings deposited by thermal and plasma-enhanced CVD.

Hard BCN films were deposited by chemical vapour deposition (CVD) on Si(100) substrates. TCVD (thermal activated) and PECVD (GD or RF microwave plasma-activated, respectively) were used. The films were analysed with respect to chemical state, composition, morphology and microstructure, oxidation behaviour and hardness. Wavelength dispersive X-ray spectroscopy (EPMA), infrared spectroscopy (IR), transmission electron microscopy (TEM), differential thermal analysis (DTA) and hardness evaluation were employed for film characterization. A correlation between deposition parameters and film composition, structure and hardness could be proved in every CVD process. Parallels between TCVD and PECVD films emerged in the case of chemical composition and the correlation between carbon content and hardness values. Considerable differences exist with regard to the microstructure, especially the texture of the films. Moreover in TCVD films the carbon is preferentially incorporated between the BN basal planes, whereas in PECVD films it is incorporated preferentially in as well as between the BN basal planes.

Journal Article↗
PubMed2003

Fluid therapy in sepsis with capillary leakage.

Sepsis is associated with a profound intravascular fluid deficit due to vasodilatation, venous pooling and capillary leakage. Fluid therapy is aimed at restoration of intravascular volume status, haemodynamic stability and organ perfusion. Circulatory stability following fluid resuscitation is usually achieved in the septic patient at the expense of tissue oedema formation that may significantly influence vital organ function. The type of fluid therapy, crystalloid or colloid, in sepsis with capillary leakage remains an area of intensive and controversial discussion. The current understanding of the physiology of increased microvascular permeability in health and sepsis is incomplete. Furthermore, there is a lack of appropriate clinical study end-points for fluid resuscitation. This review considers critically the clinical and experimental data analysing the assessment of capillary leakage in sepsis and investigating the effects of different fluid types on increased microvascular permeability in sepsis.

Capillary Leak Syndrome↗
PubMed2003

[Massive transfusion of washed red blood cells: acid-base and electrolyth changes for different wash solutions].

OBJECTIVE: The composition of normal saline (NaCl), the standard wash solution for cell saver autotransfusion, is considerably different from physiologic plasma values in small infants. Therefore, we investigated acid-base and electrolyte changes during massive cell saver autotransfusion with different wash solutions in young pigs. METHODS: After approval by the animal protection authorities 15 young pigs (weight 10.6 +/- 1.1 kg, blood volume 848 +/- 88 ml, mean+/-SD) underwent 15 cycles of cell saver autotransfusion (Haemolite 2plus, Haemonetics). For each cycle, 100 ml arterial blood was withdrawn, washed with NaCl, physiologic multielectrolyte solution (PME, V Infusionslösung 296 mval Elektrolyte, Baxter) or physiologic erythrocyte protection solution (PEP, 3.2 % gelatine, pH 7.40, cHCO3 24 mmol/l), and then retransfused. Analyses of acid-base, electrolyte, and hematologic parameters were performed for systemic and washed blood samples. RESULTS: For NaCl there was a progressive decrease in systemic pH, HCO3 and base excess (BE) and an increase in chloride values (Cl) (p < 0.05). Use of PME slightly decreased pH (n. s.), whereas HCO3, BE and Cl remained stable. PEP slightly increased pH, HCO3 and BE, and decreased Cl (n. s.). Free hemoglobin increased in NaCl and PME (p < 0.05) and was below baseline in PEP (n. s.). Lactic acid course was comparable in all groups. CONCLUSIONS: The use of NaCl as wash solution for massive autotransfusion resulted in metabolic acidosis caused by dilution of HCO3 and increased Cl values. Fewer systemic acid-base and electrolyte changes were observed, when blood was washed with PME or PEP. The decreased hemoglobin release with PEP is possibly due to a gelatine specific electrostatic surface coating of erythrocyte membranes. For massive transfusion of washed red blood cells, physiologic multielectrolyte solution and physiologic erythrocyte protection solution should be preferred to NaCl, especially for small infants.

Acid-Base Equilibrium↗