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Biomedical subjects

G Schlag

Publications and source records attributed to G Schlag.

At least 73 records · Page 4Linked to original sources
PubMed1995

Acute lung injury by endotoxin-induced mediators: prevention by HWA 138, a new xanthine derivative.

We attempted to mimic septic conditions in vitro by using a model of isolated perfused rabbit lung (IPRL) and evaluated the effects of endotoxin or endotoxin-induced mediators (or both) on it. Moreover, we determined the salutary effects of HWA 138, a new xanthine derivative, against endotoxin-related lung injury. To study this, heparinized human blood was centrifuged, following which the plasma complement was inactivated by heat treatment and the isolated and washed buffy coat cells were then added to it. This was followed by incubation of aliquot suspension with and without endotoxin (lipopolysaccharide [LPS], 100 ng/ml) at 37 degrees C for 2 hours. Plasma was then harvested and is referred to as sepsis-like plasma (SLP). Control plasma (CP) was not exposed to LPS. IPRLs were then perfused with SLP, CP, LPS itself, or both LPS and CP without additional white blood cells. Endotoxin itself did not induce any changes in the presence or in the absence of control plasma; however, sepsis-like plasma led to the development of lung edema, as evidenced by significantly elevated lung water and pulmonary artery pressure. Administration of HWA 138 before the addition of SLP prevented the SLP-induced lung injury. These results lead us to conclude that lung injury is caused by LPS-induced mediators rather than being directly caused by LPS. The results also suggest that HWA 138 may be a useful agent in the treatment of sepsis-induced pulmonary injury.

Animals↗
PubMed1995

[Monitoring of bone marrow spilling and cardiopulmonary changes in fat embolism syndrome].

After long bone fractures, as well as hip or knee total arthroplasty, the increase in intramedullary pressure induces bone marrow release into the circulation in more than 90% of patients. Three to four percent of the patients reveal fat embolism syndrome with pulmonary and cerebral involvement and a petechial rash. In about 20% of these patients a fulminant and fatal course is possible. Although fat embolism syndrome was described more than a century ago, there is still no sufficient therapeutic strategy. Because of these facts we try to prevent fat embolism syndrome and monitor patients at risk perioperatively. We have evaluated different diagnostic methods and monitoring facilities and recommend pulse oximetry, capnography, ECG, blood pressure controls and, if indicated, blood gas analyses for perioperative monitoring. Patients at risk and patients who are suffering from fat embolism syndrome require more intensive monitoring, such as transesophageal echocardiography and a pulmonary artery catheter to obtain more detailed information about the hemodynamic and oximetric variables. Furthermore, these patients must be admitted to an intensive care unit.

Blood Gas Analysis↗
PubMed1995

[Modified surgical technique for reduction of bone marrow spilling in cement-free hip endoprosthesis].

Since 1970 the fat embolism syndrome (FES) has been recognised as a severe complication of cemented total hip arthroplasty (THA). Initially and still today the toxicity of bone cement has been though to be responsible for the cardiorespiratory problems. Meanwhile several reports have confirmed the causal relationship between intramedullary pressure (IMP), bone-marrow release into the circulation and subsequent cardiorespiratory deterioration during cemented THA. In recent publications it has been reported that bone-marrow release due to increased IMP also occurs during cementless THA. The clinical implication of these observations is controversial. For this reason in the first part of this paper two autopsy-proven FES deaths and five further clinically manifest FES cases are presented. In the second part of the study, IMP courses during four different surgical techniques (2 conventional, 2 modified) are compared. The aim of the modified surgical technique developed in our department was to minimize IMP peaks and bone-marrow release during cementless THA. Both modified techniques showed significantly lower IMPs during opening of the medullary canal, preparation with rasps, and implantation of the prosthesis than the conventional techniques. The observed FES cases for the first time strongly confirm the clinical relevance of the FES, also during cementless THA. On the basis of the data presented we recommend the modified surgical technique to reduce bone-marrow release during cementless THA.

Aged↗
PubMed1995

[Modified surgical technique for the reduction of bone marrow spilling in knee endoprosthesis].

In the literature 20 cases of fat embolism syndrome (FES) after total knee replacement (TKR) are reported; 16 cases had cemented hinged TKR and 4 resurfacing TKR. Initially, it was believed that the bone cement was responsible for the FES. Since then, however, Fahmy et al. have published extraordinary data, demonstrating the causal relationship between increased intramedullary pressure (IMP) during the insertion of the intramedullary rod (IR) and cardiorespiratory deterioration. The industry responded by developing a fluted IR, disregarding the overdrilling in the distal femur required by Fahmy. In the first part of this paper clinically manifest FES cases after resurfacing TKR are reported. In the second part of the study the conventional surgical technique is compared with a modified technique, which focuses on a reduction of bone-marrow release into the circulation. In the conventional and the modified group, IRs with and without flutes were compared. It was shown that only the opening of the intramedullary canal and insertion of the IR generated relevant IMP peaks during implantation of resurfacing TKR. When compared with the conventional surgical technique, the modified technique revealed significantly lower IMPs, and in neither group was a difference demonstrated between the IR with or without flutes. In 4 patients (2 conventional, 2 modified) transesophageal echocardiography (TEE) was performed for detection of bone-marrow release into the circulation. In the two patients operated on conventionally, TEE showed a markedly higher bone-marrow release than in the patients with modified operations. In conclusion, we recommend the presented modified surgical technique in order to reduce bone-marrow release into the circulation.

Aged↗
PubMed1995

[Therapeutic approach to the management of fat embolism syndrome].

So far, no clinical or experimental study has demonstrated that any drug has a beneficial effect (heparin, cortisone, dextran, etc.) on the course of fat embolism syndrome (FES). Thus, prevention, early diagnosis, and adequate symptomatic treatment are of paramount importance. Besides surgical measures, such as reduction of intraosseous pressure and bone-marrow release during hip or knee replacement, proper treatment of shock in traumatized patients, recognition of risk factors and maintainance of intraoperative cardiorespiratory stability are cornerstones in the prevention of fat embolism syndrome. It is well documented that bone-marrow release into the circulation and pulmonary embolism occurs during any hip or knee arthroplasty. As a result of improvements in anesthesia management, the clinical appearance of FES has moved into the postoperative period. This calls for mandatory cardiorespiratory monitoring up to 24 h postoperatively. When facing a clinically manifest fat embolism syndrome, monitoring and symptomatic treatment must be adapted to the patient's needs in order to ensure adequate oxygenation and acceptable circulatory conditions to protect organ function.

Catheterization, Swan-Ganz↗
PubMed1995

[Pathophysiology of fat embolisms in orthopedics and traumatology].

It is well known that fat embolisms can occur after long bone fractures, and this has been feared for more than 100 years. Since 1970 fat embolisms have also been recognized in endoprosthetic surgery. The clinical manifestation was described as the fat embolism syndrome (FES) by Gurd in 1974. Based on reports in the literature and our own data, a concise pathophysiological model of the FES is presented in this paper. The increase in intramedullary pressure (IMP) in the long bones is the most decisive pathogenic factor for the development of an FES. Any long bone fracture, stabilization of fractures, or implantation of knee or hip endoprostheses can generate IMP peaks leading to bone marrow release into the circulation. Bone marrow itself is a tremendous stimulus for activation of the clotting system. As a result, hypercoagulation and venous stasis in the draining veins generate mixed macroemboli from the initial bone-marrow microemboli. Bone-marrow embolization of the lung in phase I leads to mechanical obstruction of pulmonary arteries. In phase II, release of local mediators, triggered by a systemic inflammatory response (SIR) of the lungs, causes damage to the pulmonary membranes. Disturbed gas exchange and respiratory insufficiency with possible cardiac and cerebral decompensation are the result. In most cases an FES may not be detected clinically, and any mild cardiorespiratory changes are treated easily with oxygen insufflation and usually disappear within 48 h. Of paramount importance for clinical manifestation of an FES are the quantity and duration of bone-marrow release and co-factors (cardiorespiratory compliance and perioperative stability of the patient). Patients with preexisting cardiorespiratory disease in combination with massive intraoperative bone-marrow release may even face a deadly FES event. Increased IMP causes local obstruction of cortical vessels with bone marrow. In combination with the damaged endosteal blood supply, avascular necrosis of the cortical bone occurs. During endoprosthetic procedures, mechanical-and mediator-triggered damage of the intima of big veins, in combination with venous stasis and hypercoagulation may be responsible for the high incidence of proximal thrombosis of femoral veins. As a delayed result of the disseminated intravascular coagulopathy, petechial bleeding in the trunk and subconjunctiva can be seen. A better understanding and recognition of the FES's pathophysiology may help to use prophylactic, diagnostic and therapeutical measures more effectively.

Blood Coagulation↗
PubMed1995

Effect of anti-tumor necrosis factor alpha on leukocyte adhesion in the liver after hemorrhagic shock: an intravital microscopic study in the rat.

Tumor necrosis factor (TNF) plays a well known role during the development of multiple organ failure, in part due to its role for the expression of adhesion molecules on endothelial cells, thereby contributing to inflammatory reactions. The purpose of this study was to investigate the effects of TNF on leukocyte-endothelial interactions in the liver as a key organ during the systemic inflammatory response syndrome. In Sprague-Dawley rats (n = 6/group) hemorrhagic shock was induced by reduction of the mean arterial blood pressure (MAP) to 40 mmHg for 45 min; resuscitation was initiated by retransfusion of shed blood (60%) and Ringer's lactate. At 1 and 5 h after resuscitation, intravital microscopy of the liver was performed after injection of acridine orange as marker of leukocytes in sham-control animals and in shock animals pretreated with anti-TNF monoclonal antibody (2 mg/kg b.w. TN3; Celltech, Slough, UK) or NaCl .9% 2 h prior to shock induction, respectively. At constant systemic hemodynamic conditions in all groups (e.g., normal MAP), sinusoidal diameters and sinusoidal blood flow were comparably decreased to approximately 75% of control values in all shock groups. Significant differences were observed particularly in respect to permanent adherent leukocytes with 31.8 +/- 4.7% in the shock/NaCl group and 20.7 +/- 2.6% (mean +/- S.E., p < .05) in the shock/TN3 group 5 h after resuscitation following hemorrhagic shock. Consistently higher adhesion rates were observed in the portal regions compared to pericentral regions of the liver lobules.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Biocompatibility of xenogeneic bone, commercially available coral, a bioceramic and tissue sealant for human osteoblasts.

The drawbacks of freshly harvested autologous bone have resulted in the search for an alternative, capable of supporting osteogenic cell growth. This capability was examined in potential bone graft materials by culturing human osteoblasts on each material. Test materials included rat bone, Surgibone, Ostilit, Biocoral and Tisseel. After 3 days osteoblasts had adhered to all materials, except Ostilit. With increasing time the cells multiplied on the materials, to varying extents. Cell affinity was greatest for rat bone and Tisseel. Fewer cells attached to Biocoral and Surgibone. Thus all the materials, with the exception of Ostilit, were biocompatible for human osteoblasts.

Animals↗
PubMed1994

Formation of cytokines by retransfusion of shed whole blood.

We have studied, in 10 patients undergoing hip replacement surgery, the release of cytokines (tumour necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-alpha), interleukin-1 beta (IL-1 beta), interleukin-4 (IL-4), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in association with retransfusion of autologous shed blood. The patients were reinfused with whole blood collected after operation. The median volume returned to the patients was 300 ml whole blood (25-75% range = 300-425 ml). Before reinfusion, blood was filtered. Plasma concentrations of IL-6 increased 1 and 60 min after retransfusion (P < 0.05). The plasma concentrations of TNF-alpha, IL-1 alpha, IL-1 beta, IL-4 and IL-8 did not change significantly after retransfusion of shed wound blood. However, there were increased concentrations of IL-1 alpha, IL-1 beta, IL-6 and IL-8 in the collected blood (P < 0.001). The filtration procedure did not reduce significantly the concentrations of these factors. This study shows that whole blood collected from a surgical wound contains large concentrations of cytokines. Filtration of the shed wound blood did not reduce significantly these levels and retransfusion caused increased plasma concentrations of IL-6.

Aged↗
PubMed1994

Intramedullary pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep.

In this study, intramedullary reaming and nailing were performed following the insertion of pressure transducers in intact tibias and femora. The femur and tibia were instrumented in 12 sheep (group I) and both tibiae in four (group II). The eight procedures of group II were monitored additionally using echocardiography to detect emboli. Intravasation of fat globules was demonstrated in the blood by the Gurd test and correlated with intramedullary pressure and with echocardiographic monitoring in group II. Medullary nailing was found to be always associated with a severe increase in intramedullary pressure, reaching an average of 1126 mm Hg (304 to 1450 mm Hg) in the tibia and of 753 mm Hg (310 to 1126 mm Hg) in the femur during the first reaming procedures. Particle or fat intravasation was greatest during nail insertion. This phenomenon did not depend on the rise in intramedullary pressure. Our findings indicate that fat and bone marrow intravasation occurs during reaming and nailing in long bones. The maximum embolization of marrow contents demonstrated by echocardiography is seen during nail insertion independent of the changes in intramedullary pressure.

Animals↗
PubMed1994

Pulmonary reaction during intramedullary fracture management in traumatic shock: an experimental study.

Immediate nailing of shaft fractures in severely injured patients causes fat embolization. This method therefore is considered potentially dangerous, since fat intravasation in association with multiple trauma and subsequent endotoxemia might lead to pulmonary dysfunction. We therefore studied the pathophysiologic events of intramedullary nailing in the lungs of sheep with chronic instrumentation including lung lymph fistula. In the 7 animals in group I closed nailing of the intact tibia and femur was performed. Group II (n = 7) animals sustained hypovolemic shock and retransfusion prior to nailing, while group III (n = 11) animals were treated like those in group II and further challenged on the following two days with endotoxin. Group III was compared with group IV (n = 6), in which endotoxin was given only once without additional trauma. Nailing in group I led to a significant increase of the MPAP from 10.8 to 13.8 mm Hg postoperatively (p < 0.05), but no increase in lung permeability. Only additional hypovolemia, retransfusion and nailing as performed in groups II and III showed significant increase of the lymph flow (QI) from 4.4 mL/h to 12.4 mL/h and the protein clearance (Pclear) from 3 to 6.3. A significant difference of the pulmonary permeability between group I and II was only observed postoperatively. There was no difference in the lung response between group III and IV. This ovine study corroborates that although nailing causes a moderate increase in pulmonary pressure, it does not lead to increased lung permeability. Only additional hemorrhagic shock, even when adequately resuscitated, leads to lung disturbance postoperatively. The subsequent endotoxin challenge does not aggravate lung injury.

Animals↗
PubMed1994

A noninvasive functional evaluation following peripheral nerve repair with electromyography in a rat model.

A new bipolar surface electrode array was designed and constructed for a noninvasive "closed" functional evaluation with electromyography following sciatic nerve transection in a rat model. This "closed" method was compared with a conventional one-shot "open" measurement. Nerve conduction velocity and distal latency were calculated. Data obtained from the recordings from different animals as well as from the same animal at different points in time yielded excellent reproducibilities. There is no difference in the mean values whether nerve conduction velocity and distal latency are obtained by "closed" or "open" measurements. Correlation was significant (p < 0.01; rNCV = 0.77, rDL = 0.63) between these two methods. The results lead to the conclusion that the noninvasive functional evaluation with the parameters of nerve conduction velocity and distal latency introduced in the present study could be employed as a reliable method for serial functional evaluations following nerve transection in a long-term study in a rat model.

Animals↗
PubMed1994

Myocardial function in septic sheep.

There is an ongoing discussion whether the heart is the primary target organ responsible for the development of cardiovascular failure during septic shock as well as its onset. We tried to study the reaction of the heart to sepsis in the early phase of 8 h, using a sublethal model of sepsis in six awake cross-bred Austrian mountain sheep. Sepsis was induced by infusion of a live Escherichia coli suspension at a dose of 5 x 10(7) colony-forming units per kg body weight over 8 h. Standard hemodynamic, hematologic and serum tumor necrosis factor (TNF) measurements were obtained. For evaluation of left ventricular performance we used the following methods, tested in five pilot experiments: 1) The shift of the end-systolic pressure-diameter relation. This was characterized by the calculated shift of the transverse external end-systolic diameter of the left ventricle at a "midrange" end-systolic pressure of 100 mmHg (end-systolic ventricular diameter deviation, ESVDD100). Calculations were performed using a second order regression function of the end-systolic pressure diameter points obtained by variation of afterload by a cuff occluder on the aorta; 2) The shift of the (dP/dt)max over end-diastolic diameter ratio compared to control values estimated by a graphical approach. Mean pulmonary pressure increased from 21 +/- 1 to 36 +/- 2 mmHg in the first hour after starting the E. coli infusion and remained elevated during the entire 8 h observation period. Serum TNF was found to peak 1 hour after start of E. coli infusion and was hardly detectable after 3 hours of bacteremia. Mean aortic pressure showed minor changes (maximum 105 +/- 3 mmHg, minimum 91 +/- 2 mmHg) and there were no statistically significant alterations of the cardiac index. ESVDD100 showed an "oscillatory" reaction in the first phase and a statistically significant decrease of contractility in the second phase (at 4 h). This was confirmed by the graphical method of the (dP/dt)max over end-diastolic diameter ratio. We may therefore conclude that there is no early depression of myocardial function or if so, it may be masked by adrenergic stimulation. In the later phase of the 8 h experiment there is a significantly decreased contractility of the heart. This may be compensated (e.g., "Starling" mechanism or heart rate increase) in this sublethal model.

Animals↗
PubMed1994

Anti-tumor necrosis factor antibody treatment of recurrent bacteremia in a baboon model.

Timely intervention in recurrent episodes of sepsis poses a major problem in intensive care, because the diagnosis is often made after the onset of sepsis, delaying the initiation of treatment. There are only a few animal models that cover this situation. We have developed a baboon model of recurrent bacteremia (3 x 2 h intravenous infusion of 1 x 10(8) CFU Escherichia coli/kg), which leads to late organ failure. In this model (tested on 16 animals) we began anti-tumor necrosis factor antibody treatment (BAYX 1351; Bayer AG, 7.5 mg/kg or saline placebo) after the first bacteremic episode (+4 h), which significantly (p < .05) protected animals from death, none out of eight (100% survival), in the treatment group in contrast to four animals out of eight died (50% survival) in the placebo group. This effect was also reflected in improved organ function and in attenuated cytokine and plasminogen activator inhibitor release. From these studies we conclude that the delayed application of anti-tumor necrosis factor antibodies in recurrent bacteremia is a powerful tool for preventing septic death.

Animals↗
PubMed1994

Similar cytokine but different coagulation responses to lipopolysaccharide injection in D-galactosamine-sensitized versus nonsensitized rats.

To compare cytokine release and coagulation disturbances induced by administration of high versus low doses of endotoxin (lipopolysaccharide [LPS]), we used two endotoxin test systems similar in mortality but different in the degree of endotoxemia. One group of rats (n = 11) randomly received endotoxin (15.0 mg/kg of body weight intraperitoneally [i.p.]) and 1 ml of Ringer's solution (nonsensitized animals). The second group (n = 11) received 1 ml of D-galactosamine (500 mg/kg i.p.) and endotoxin (100 micrograms/kg i.p.) simultaneously (sensitized animals). Endotoxin levels in the plasma of nonsensitized rats were 1,000-fold higher than those in the plasma of sensitized rats (69.33 x 10(3) +/- 22.42 x 10(3) versus 75.8 +/- 27.08 ng of LPS per ml), leading to a mortality of 91% in nonsensitized rats versus 82% in the sensitized-rat model within 48 h postendotoxemia. Serum transaminase activity increased up to 100-fold in sensitized rats as a sign of hepatocyte damage. Despite the large difference in LPS levels in plasma, the time courses of the plasma tumor necrosis factor (TNF) increase were similar in the two groups, with a peak at 2 h (54 +/- 12 ng/ml in nonsensitized rats versus 43 +/- 12 ng/ml in sensitized rats), and also similar to that of a group of nonsensitized rats (n = 5) that received a low dose of LPS (100 micrograms/kg) only (52 +/- 21 ng/ml), while D-galactosamine alone did not induce TNF release. Despite similar TNF levels, a more pronounced coagulation disorder was observed at 4 h in nonsensitized rats (with the high LPS dose) as measured by platelet counts, plasma fibrinogen levels, and activated partial thromboplastin time prolongation (191 x 10(3) +/- 107 x 10(3) cells per microliter, 40 +/- 24 mg/dl, and 53 +/- 15 s, respectively) than in rats with the low LPS dose either sensitized (495 x 10(3) +/- 153 x 10(3), 95 +/- 49, and 38 +/- 16, respectively) or nonsensitized (439 x 10(3) +/- 62 x 10(3), 170 +/- 18, and 35 +/- 11, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Repeated administration of a F(ab')2 fragment of an anti-tumor necrosis factor alpha monoclonal antibody in patients with severe sepsis: effects on the cardiovascular system and cytokine levels.

In an uncontrolled clinical trial the effects of repeated administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis. Patients were treated with a total of 11 single dosages of the anti-TNF alpha-antibody intravenously over 5 days using either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). The anti-TNF alpha-antibody was well tolerated in all patients without signs of toxicity and without development of anti-murine antibodies. As assessed by cytokine levels (TNF alpha, Interleukin-6) and hemodynamics there was no evidence that the higher dosage of the anti-TNF alpha-antibody (3 mg/kg per dose) was more effective than the lower dosage (1 mg/kg per dose). Comparison of our data with recent data from phase I or II trials using a complete murine monoclonal anti-TNF alpha-antibody suggest that the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of similar efficacy. Definitive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of larger ongoing placebo-controlled trials.

Adult↗