Biomedical subjects

A Dwenger

Publications and source records attributed to A Dwenger.

At least 19 recordsLinked to original sources

PubMed2002

Treatment and prophylaxis of severe infections in neutropenic patients by granulocyte transfusions.

Bacterial and fungal infections are the main cause of morbidity and mortality in neutropenic patients. To resolve infections, an adequate number of functional granulocytes is required. Successful treatment of severe infections with granulocyte transfusions is strongly dependent on an adequate number of transfused cells. In this study, 42 neutropenic patients received rhG-CSF-stimulated granulocyte transfusions (GTXs). Of these patients, 18 with severe infections during neutropenia and 8 in a high-risk situation, as defined by severe infections during previous periods of neutropenia or increasing infectious parameters during prolonged neutropenia, received a median of three GTXs (range 1-25), containing a median total of 2.62x10(10) leukocytes (range 0.3-8.61x10(10)). A further 16 patients in a pilot study received prophylactic GTX, consisting of a median of three GTXs (range 1-4) containing a median total of 3.20x10(10) leukocytes (range 0.73-8.51x10(10)). Out of 18 patients with severe infections, 12 improved clinically or showed a resolution of infection after GTX. All 8 patients in a high-risk situation showed a stable clinical course without serious infections. Prophylactic GTX did not result in significant differences with regard to infectious parameters. The median number of transfused platelet units during the course of cytopenia was significantly reduced (13.5 units vs 22.0 units, P<0.02) compared to the control group. For the treatment of infections during neutropenia, rhG-CSF-stimulated granulocyte transfusions are safe and a promising approach.

Adolescent↗

PubMed2000

Production of stem-cell transplants according to good manufacturing practice.

Peripheral blood stem cells (PBSCs) are used for transplantation to reconstitute the hematopoietic system after high-dose chemotherapy. They are harvested from peripheral blood after mobilization by cytokines and/or chemotherapy. Further ex vivo manipulation steps (e.g., selection of CD34+ PBSCs, purging, expansion, and differentiation or gene transfer) can be performed. In 1997, more than 12,000 PBSC preparations were transplanted in Europe and the total number is steadily increasing [1]. To ensure quality and safety of the final cell products intended for clinical use, national and international guidelines and regulations have been issued. The implementation of a quality assurance (QA) program including the principles of good manufacturing practice (GMP) and a quality control system is a major requirement. GMP regulations apply to all phases of cell collection, processing, and storage, and to documentation, training of personnel, and equipment of the cell processing laboratory. They have to be followed by pharmaceutical companies and medical doctors who are involved in PBSC processing at academic institutions. The complicated regulatory network for the manufacturing of cell products will help to standardize these procedures and ensure consistent quality and safety in the long term. This will be in the interest of patients and reduce risks of application of individual cell preparations.

Clinical Laboratory Techniques↗

PubMed2000

Ascorbic acid for amelioration of reperfusion injury in a lung autotransplantation model in sheep.

BACKGROUND: Reperfusion injury is the leading cause of early graft dysfunction after lung transplantation. Activation of neutrophilic granulocytes with generation of free oxygen radicals appears to play a key role in this process. The efficacy of ascorbic acid as an antioxidant in the amelioration of reperfusion injury after lung transplantation has not been studied yet. METHODS: An in situ autotransplantation model in sheep is presented. The left lung was flushed (Euro-Collins solution) and reperfused; after 2 hours of cold storage, the right hilus was then clamped (group R [reference], n = 6). Group AA animals (n = 6) were treated with 1 g/kg ascorbic acid before reperfusion. Controls (group C, n = 6) underwent hilar preparation and instrumentation only. RESULTS: In group R, arterio-alveolar oxygen difference (AaDO2) and pulmonary vascular resistance (PVR) were significantly elevated after reperfusion. Five of 6 animals developed frank alveolar edema. All biochemical parameters showed significant PMN activation. In group AA, AaDO2, PVR, work of breathing, and the level of PMN activation were significantly lower. CONCLUSIONS: The experimental model reproduces all aspects of lung reperfusion injury reliably. Ascorbic acid was able to weaken reperfusion injury in this experimental setup.

Animals↗

PubMed1999

Amelioration of lung reperfusion injury by L- and E- selectin blockade.

OBJECTIVE: Reperfusion injury is the main reason for early graft failure after lung transplantation. Inhibition of the adherence of polymorphonuclear leukocytes to activated endothelium by blocking L- and E-selectins (antibody EL-246) could potentially inhibit reperfusion injury. METHODS: Reperfusion injury was induced in a left lung autotransplant model in sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 h in situ at 15 degrees C. After reperfusion right main bronchus and pulmonary artery were occluded leaving the animal dependent on the reperfused lung (control, n = 6). Pulmonary function was assessed by alveolo-arterial oxygen difference (AaDO2) and pulmonary vascular resistance (PVR), the chemiluminescence of isolated neutrophils, as well as the release of beta-N-acetyl-glucosaminidase (beta-NAG) served as indicator of neutrophilic activation. Extravascular lung water was an indicator for pulmonary edema formation. EL-246 group animals (n = 6) were treated additionally with 1 mg/kg BW of EL-246 given prior and during reperfusion. RESULTS: After 3 h of reperfusion five control animals developed alveolar edema compared to one animal in the EL-246 group (P = 0.08). AaDO2 (mm Hg) was significantly higher in the control compared to the EL-246 group (510 +/- 148 vs. 214 +/- 86). PVR (dyn x s x cm(-5)) was significantly increased in the control compared to the EL-246 group (656 +/- 240 vs. 317 +/- 87). Neutrophilic activation was significantly lower in the EL-246 group. Extravascular lung water was significantly lower compared to control (6.88 +/- 1.0 vs. 13.4 +/- 2.8 g/g blood-free lung weight). CONCLUSIONS: Treatment with EL-246 results in improved pulmonary function and less in vivo PMN activation in this experimental model. Further studies are necessary to evaluate the possible role of selectin blockade in amelioration of reperfusion injury in human lung transplantation.

Acetylglucosaminidase↗

PubMed1999

Quantitative lymphocyte subset reconstitution after allogeneic hematopoietic transplantation from matched related donors with CD34+ selected PBPC grafts unselected PBPC grafts or BM grafts.

CD34+ cell selection of PBPC after harvest from G-CSF-treated allogeneic donors results in a more than 200-fold depletion of T lymphocytes in the graft and has been used to reduce the incidence of acute GVHD post transplant. Since transplantation with T cell-depleted BM grafts is associated with a delay in immune reconstitution and an increase of opportunistic infections, we evaluated the immunological reconstitution of patients with hematologic malignancies after therapy followed by CD34+-selected PBPC34 transplantation from matched related donors. Lymphocyte subset reconstitution over the first 12 months post transplant and the incidence of infections were evaluated in 12 patients receiving PBPC34 grafts and compared to that of patients after transplantation with PBPC without CD34+ enrichment (n = 20) or unmanipulated bone marrow grafts (BM; n = 15). PBPC34 grafts contained 264-fold fewer T lymphocytes (median 0.53 x 10(6) kg/body weight) than PBPC grafts and 36-fold fewer than BM grafts (140 x 10(6)/kg and 19 x 10(6)/kg, respectively). Despite a two log depletion of T cells in the PBPC34 grafts, T lymphocyte reconstitution appeared comparable among the three transplant groups over the first 12 months. A positive patient CMV serostatus pretransplant was correlated with a faster T cell reconstitution in all transplant groups. GVHD prophylaxis with methylprednisolone delayed B lymphocyte reconstitution. The incidence of infections post transplant did not appear to be increased in the PBPC34 group compared with the PBPC and BMT groups. It remains to be shown in larger prospective trials, whether these promising preliminary data of lymphocyte reconstitution and the clinical course after transplantation with PBPC34 can be confirmed.

Adult↗

PubMed1998

Multiple organ failure (MOF) after severe trauma--a sheep model.

OBJECTIVE: To perform a reproducible long-term (10 days) large animal model of multiple systems organ failure without necessity of a continuous stimulus. DESIGN: Adult female merino sheep submitted to a 5-day stimulation period followed by a 5-day observation period. Day 1: Hemorrhagic shock was combined with a traumatic surgical insult (reamed intramedullary femoral nailing), followed by serial administrations every 12 h for 5 days of a combination of endotoxin and zymosan activated plasma. Organ function was followed for 5 further days. RESULTS: Cardiac index increased significantly during the study (day 1: 491 +/- 8 mm Hg; day 10: 427 +/- 20, p < 0.05). Liver function was impaired and bilirubin levels increased significantly (day 1: 2.9 +/- 0.3 micromol/l; day 10: 7.2 +/- 0.9; p < 0.05). Creatinine clearance decreased initially (day 1: 54 +/- 7 ml/min), increased to a peak on day 2 (104 +/- 27), and then deteriorated again (day 10: 53 +/- 18). CONCLUSION: This new large animal model of trauma-induced MOF is reproducible and may be suitable for the study of new therapeutic approaches to therapy.

Albumins↗

PubMed1996

Attenuation of multiple organ dysfunction in a chronic sheep model by the 21-aminosteroid U74389G.

Animal studies have shown that 21-aminosteroids have beneficial effects on cell and organ functions in several acute models of traumatic, hemorrhagic, and septic shock. However, it is not known if the 21-aminosteroid U74389G has any beneficial effect on organ functions in a recently developed chronic sheep model of multiple organ dysfunction after trauma. Furthermore, it is not known whether this drug has any effect on in vivo leukocyte function in this animal model. To study this, anesthetized animals were subjected to hemorrhagic shock (2 hr at a mean arterial blood pressure of 50 mmHg) and femoral reaming at Day 0. The following 5 days, endotoxin (ET; 0.75 micrograms/kg BW) and zymosan-activated plasma (ZAP; 20 ml/animal) were given every 12 hr. During the third phase (Days 6-10), the animals were merely observed. This kind of model resulted in progressive organ dysfunction indicated by increased cardiac output, decreased systemic vascular resistance, an increase of plasma-sorbitoldehydrogenase, impaired bilirubin metabolism, and impaired renal and lung function in nontreated animals. Animals receiving U74389G (3 mg/kg BW) during resuscitation from hemorrhagic shock and each time before ET/ZAP administration showed less severe organ dysfunction. Furthermore, U74389G showed beneficial effects on lung function, although it had no effect on accumulation of leukocytes in the lung or on the chemiluminescence response of isolated leukocytes from bronchoalveolar lavage fluid. These results suggest that U74389G may be a useful therapeutic agent in the prevention of multiple organ dysfunction after hemorrhagic and traumatic shock.

Alanine Transaminase↗

PubMed1996

Minimal residual disease: detection, clinical relevance, and treatment strategies.

Improvement of established treatment strategies for cancer has resulted in increased survival times for patients with malignancies. However, success of surgery, chemotherapy, and radiotherapy is limited, as even combined and repeated therapy regimens and high-dose chemotherapy can only reduce tumor burden by several logarithmic steps and are not able to completely eradicate all neoplastic cells. If clinically complete remission is achieved--that is, if no sign of the tumor is detectable by standard diagnostic procedures, remaining minimal residual disease (MRD) can eventually give rise to clinically manifest relapse. More sensitive methods are, therefore, necessary to detect single tumor cells for exact staging, to assess the metastatic potential of an individual tumor, to evaluate the sensitivity to prior therapy, and to detect MRD-positive patients with remaining malignant cells who are at higher risk for relapse. Novel treatment approaches must be created to eradicate minimal residual disease after conventional therapy.

Humans↗

PubMed1996

Aprotinin prevents the development of the trauma-induced multiple organ failure in a chronic sheep model.

Trauma-induced multiple organ failure in sheep was prevented by aprotinin therapy. Multiple organ failure was induced in 16 female merino sheep by initial haemorrhagic shock and intramedullary femoral nailing (day 0), and 12 hourly injections of 0.75 micrograms/kg Escherichia coli endotoxin +0.7 ml/kg zymosan-activated plasma (days 1-5). In addition, the aprotinin group (n = 6) received simultaneous injections of 5 mg/kg (35 695 KIU/kg) aprotinin, whereas ten animals did not receive aprotinin and served as the control group (n = 10). Organ functions were monitored for a total of 11 days by measuring haemodynamic, cardio-respiratory and biochemical quantities of blood, urine and epithelial lining fluid. During the subsequent eleven day period, aprotinin induced a significant (p < 0.05) reduction of the pathological changes (development of multiple organ failure) seen in the control group. Thus, aprotinin prevented an alteration of cardiac function (cardiac index for control/aprotinin groups at day 1: 6.5/6.2, and at day 10: 10.47/7.0 1/min x m2), an impairment of lung function (mean pulmonary arterial pressure at day 1: 2.26/1.86, and at day 10: 3.83/2.13 kPa; epithelial lining fluid/plasma ratio of albumin concentrations as a direct marker of lung capillary permeability damage at day 0: 0.18/0.16, and at day 10: 0.45/0.15), a deterioration of liver function (plasma sorbitol dehydrogenase at day 0: 7.9/7.6, and at day 10: 29.6/7.4 U/1), but not of renal function (creatinine clearance at day 1: 91.4/66.1, and at day 10: 53.1/59.2 ml/min). Urinary aprotinin excretion increased up to day 3, then decreased rapidly despite further aprotinin administration. As a non-specific marker of cell damage, plasma lactate dehydrogenase indicated an aprotinin-induced organ protection (day 0: 501/409, and at day 10: 719/329 U/1). The neutrophil count and the measured chemiluminescence of neutrophils from the blood and epithelial lining fluid showed that aprotinin reduced the in vivo neutrophil activation, the alveolar neutrophil invasion, the production of inflammatory mediators, and the production of reactive oxygen metabolites during the passage of the capillary-interstitial-alveolar space by neutrophils.

Animals↗

PubMed1995

Supplementation of hypercholesterolaemic rabbits with L-arginine reduces the vascular release of superoxide anions and restores NO production.

L-arginine, the precursor of endogenous nitric oxide (NO), has been shown to enhance endothelial function and to reduce intimal plaque area in cholesterol (Chol)-fed rabbits. We have studied endogenous NO production in such animals in vitro (endothelium-dependent relaxations) and in vivo (assessed by urinary NO3- excretion) before and during chronic oral administration of L-arginine and inhibitor of NO synthesis, L-NAME. Vascular superoxide anion (O2-) production of aortic rings was measured under basal conditions and following exposure to phorbol-myristate-acetate (PMA). Cholesterol feeding reduced endothelium-dependent relaxations and decreased urinary NO3- excretion. These effects were potentiated by administration of L-NAME. L-arginine partly restored endothelium-dependent relaxations and increased NO3- excretion. PMA-stimulated O2- production was increased in aortic rings from rabbits given cholesterol ( +159 +/- 28%; mean +/- S.E.M.) or cholesterol + L-NAME ( +149 +/- 37%) as compared with controls ( -22 +/- 7%). In rabbits given cholesterol + L-arginine, O2- production was decreased to control levels ( +14 +/- 17%; P < 0.05). We conclude that the systemic synthesis of NO is impaired in cholesterol-fed rabbits, as indicated by the decreased urinary excretion of NO3-. Enhanced O2- production may further contribute to the decreased biological activity of NO in hypercholesterolaemia. L-arginine restores endothelial function in hypercholesterolaemia by enhancing NO production and by protecting NO from early breakdown by O2-.

Acetylcholine↗

PubMed1995

[Effect of primary fracture management on craniocerebral trauma in polytrauma. An animal experiment study].

Severe head trauma (BI) associated with long bone fractures is present in about 60% of polytraumatized patients admitted to hospital. However, there is no consensus regarding early fracture stabilization in such patients. In an experimental sheep study, the influence of intramedullary nailing of the femur (IMNF) on a cold-induced, vasogenic brain edema (method of Klatzo) in combination with traumatic hemorrhagic shock (THS) was investigated. Three animal groups (n = 6) were explored: group A, only BI; group B, BI and THS; group C, BI, THS and IMNF. The animals remained intubated, on controlled ventilation, sedated and received analgesia during the whole experiment. For a period of 6 h after the cold-induced brain injury the hemodynamic changes were measured and the intracranial pressure (ICP) was recorded in the left and the right hemisphere continuously. The hemorrhagic shock (MAP = 60 mm Hg) was maintained over 1.5 h. At the end of the reperfusion period (2 h) the nailing of the femur was performed. The animals were killed and the percentage water content of the brain was determined and compared with the brain water content of a control group (n = 6). There were no significant differences in ICP between groups A, B and C before or after IMNF, but in group C the ICP increased significantly after nailing. Brain water content in group C was significantly higher than in the control group and slightly significantly higher than in groups A and B. Brain edema and ICP are increased by IMNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Intramedullary femoral nailing in sheep: does severe injury predispose to pulmonary dysfunction?

OBJECTIVE: To find out if intramedullary nailing affects lung function and microvascular permeability whether or not the lung is already injured; if so whether a different method of fixation would diminish the effect; and are the pathogenetic changes related to mechanisms known to precipitate adult respiratory distress syndrome? DESIGN: Experimental study. SETTING: University hospital, Germany. MATERIAL: 29 Adult female merino sheep. INTERVENTIONS: Chronic lung lymph fistulas were created. Two of the three groups (1 and 3) underwent right sided lung contusion and haemorrhage to a mean blood pressure of 50 mm Hg for 2 hours. On day 3 groups 1 and 2 underwent intramedullary nailing, and group 3 had external fixators applied. MAIN OUTCOME MEASURES: Pulmonary arterial pressure, concentrations of triglycerides, chemiluminescence of isolated polymorphonuclear leucocytes (PMN), lymph flow, microvascular pressure, filtration coefficient, and permeability. RESULTS: Intramedullary nailing caused a transient significant increase in pulmonary arterial pressure and triglycerides in groups 1 and 2. Chemiluminescence of isolated PMN decreased in group 1 and increased in group 2. Lymph flow increased 2.5 times in group 1 while microvascular pressure decreased; in group 2 the increase was less but microvascular pressure increased. Filtration coefficient in group 1 was five times that of group 2 and there was a twofold increase in permeability. There were no changes in group 3. CONCLUSION: Intramedullary nailing causes additional damage to lungs after lung damage and haemorrhagic shock in sheep. This can be avoided if (in the presence of additional injuries) alternative methods are used.

Animals↗

PubMed1995

[A standardized large animal model of multiple organ failure after severe trauma].

In the past various attempts have been made to develop a standardized animal model of multiple organ failure (MOF). Until now there has been no large animal model, that imitates the clinical situation of multiple trauma patients up to MOF. In a manner similar to the pathophysiological sequence in multiple trauma patients, the combination of damaging mechanisms in the early phase (hemorrhagic shock, operating trauma, application of endotoxin (ET; 0.75 microgram/kg body weight) and zymosan-activated plasma (ZAP; 20 ml) every 12 h on days 1-5) leads to sequential irreversible damage to several organs in the late phase (> day 6) in sheep (n = 10). In this animal model representative organ parameters showed a similar course to that in MOF after multiple trauma in humans. The cardiac index increased significantly in the late phase (day 1: 6.47 +/- 0.41 ml/min x m2; day 10: 10.36 +/- 0.79 ml/min x m2), arterial oxygen pressure declined significantly (day 1: 103.1 +/- 1.6 mmHg; day 10: 89.8 +/- 4.2 mmHg). Liver function was impaired, bilirubin levels showed a significant increase (day 1: 2.94 +/- 0.34 mumol/l; day 10: 7.19 +/- 0.91 mumol/l). Creatinine clearance was low on day 1 (54.3 +/- 7.4 ml/min), increased up to day 5 and deteriorated again significantly in the late phase over the entire period (day 2: 104.3 +/- 26.8 ml/min; day 10: 53.1 +/- 17.6 ml/min).

Animals↗

PubMed1994

Increased gut permeability after multiple trauma.

Gut permeability was studied in multiply injured patients with respect to the development of multiple organ failure (MOF). Two groups were defined according to MOF score (threshold 10 points) as to whether MOF developed (group 1; n = 11, four deaths) or did not (group 2; n = 21, no death). Gut permeability was determined from the ratio of urinary excretion of enterally administered lactulose and mannitol. Serum elastase concentrations were also determined. Mean(s.e.m.) gut permeability was abnormal during the entire study (day 1: group 1--5.1(2.1) versus group 2--10.6(4.1) (P not significant; P < 0.001 versus normal volunteers, 0.56(0.24)). An increase on days 3 and 5 correlated with serum elastase levels only in patients in group 1 (rs = 0.71, P < 0.01). Severe injury leads to increased intestinal permeability, which is related to a systemic inflammatory response.

Adult↗

PubMed1994

The basal and stimulated release of the endothelium-derived relaxing factor from isolated pig coronary arteries does not interfere with the vascular release of superoxide.

Oxygen-derived free radicals, in particular superoxide anions, are known to inactivate the endogenous vasodilator endothelium-derived relaxing factor (EDRF) which is probably identical with the gaseous radical nitric oxide. It is possible that EDRF is not the target of superoxide anions but may also be an endogenous scavenger of this radical. Superoxide anions generated by the vessel wall were measured by a modified lucigenin-enhanced chemiluminescence technique in isolated pig coronary artery rings with intact endothelium. The addition of bovine superoxide dismutase, a scavenger of superoxide anions, decreased the chemiluminescence signal by 40 +/- 26% (mean +/- SD; P < 0.05; n = 21) indicating reduced generation/release of superoxide anions. In contrast, pretreatment of coronary artery rings with diethyldithiocarbamate, an inhibitor of the intrinsic copper-zinc superoxide dismutase, increased the chemiluminescence response by 136 +/- 128% (P < 0.05; n = 21). This increase in the chemiluminescence response induced by diethyldithiocarbamate-pretreatment was almost abolished in the presence of added bovine superoxide dismutase. Specific inhibition of the EDRF release with nitro-L-arginine (100 microM) did not affect the chemiluminescence response. On the other hand, stimulation of the EDRF release by substance P (10 nM) or addition of the endothelium-mediated relaxant bradykinin (0.1 microM) did not affect the chemiluminescence response. Stimulation of the EDRF release with serotonin (0.1 microM) significantly reduced the photon emission by 15 +/- 16% (n = 27).(ABSTRACT TRUNCATED AT 250 WORDS)

Acridines↗

PubMed1994

Does the reamer type influence the degree of lung dysfunction after femoral nailing following severe trauma? An animal study.

In multiple trauma patients with lung contusion, pulmonary complications have been reported that were attributed to intramedullary stabilization of the femur. The reaming procedure of the medullary canal is thought to play a major role. We investigated whether different types of reamers might exert different amounts of fat mobilization into the vascular system and different degrees of pulmonary dysfunction. Adult female Merino sheep were submitted to hemorrhagic shock (2 h, 50 mm Hg) and a unilateral lung contusion; in addition, a lung lymph fistula was created. Pulmonary capillary permeability, central venous triglyceride levels, 11-dehydro-thromboxane B2 (dh-TXB2) levels, and pulmonary artery pressure were determined. After recovery, animals were randomly assigned to intramedullary femoral nailing using several types of reamers: group A, AO reamer (n = 8); group B, Biomet reamer (n = 7); group H, Howmedica reamer (n = 6); group C, controls, no reaming (n = 4). Intramedullary reaming caused a significant (p < 0.05) increase in pulmonary artery pressure in groups A and B; dh-TXB2 levels increased in all groups. Statistically significant (p < 0.05) pulmonary capillary permeability damage was measured in group A only. Intramedullary femoral nailing can cause transient pulmonary hemodynamic and mediator effects as well as increased pulmonary capillary permeability. In the present study, this effect was evident in group A reamer systems only, which may be due to reamer construction.

Animals↗

PubMed1994

Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits.

Production/release of superoxide anions from aortic rings was measured by a modified lucigenin-enhanced chemiluminescence (CL) technique. The aortic rings were obtained from control and cholesterol-fed (1% for 12 weeks) rabbits. The CL signal was significantly increased in aortic wall of cholesterol-fed rabbits. Pretreatment with oxypurinol, an inhibitor of xanthine oxidase, had a slight but insignificant effect on the CL response produced by aortic rings from control animals but significantly reduced CL response to aortic rings from cholesterol-fed rabbits. Pretreatment with diethyldithiocarbamate (DETC), an inhibitor of intrinsic superoxide dismutase (SOD), increased the CL signal for both animal groups, but this increase was greatly aggravated in aortic rings from hypercholesterolemic rabbits. Addition of phorbol 12-myristate 13 acetate (PMA) to stimulate the respiratory burst of wall-adherent and/or resident leukocytes had only slight effect on the CL response to aortic rings from control animals but extensively stimulated photon emission of aortic rings from cholesterol-fed rabbits. These findings are in agreement with the concept that the arterial wall in hypercholesterolemia and/or atherosclerosis is under increased "oxidative stress."

Animals↗

PubMed1994

Neuropeptide levels early after trauma: immunomodulatory effects?

The levels of endogenous opioids, beta-endorphin and methionine-enkephalin, were analyzed in 21 severely traumatized patients (ISS 32, mortality 42.8%) from a first blood sample drawn at the scene of the injury before resuscitation within 32 +/- 16 minutes after the injury and for 8 days after trauma. Additionally, the respiratory burst function of polymorphonuclear neutrophils (PMNs) was assessed and the results were compared with those obtained from 5 healthy control patients undergoing elective surgery with the same analgesic regimen as the multiple trauma patients. Compared with elective surgery anesthesia (controls 3.3, surgery 3.2 fmol/L), the beta-endorphin levels on-scene were markedly elevated (survivors 10.1 fmol/L, non-survivors 15.0 fmol/L) (p < 0.05). Methionine-enkephalin levels after trauma were not different from those of the controls. The stimulation of PMNs with different concentrations of the opioids at the first day after trauma gave results comparable with those of the controls. On the third day after trauma the reactivity of PMNs to low opioid concentrations was markedly suppressed to 79.6% of the baseline value (p < 0.05). Endogenous opioids seem to be able to modulate the nonspecific immune-response after trauma.

Adjuvants, Immunologic↗