Evaluation of S-100b as a Specific Marker for Neuronal Damage Due to Minor Head Trauma

Management of patients with minor head trauma (MHT) continues to be debated in the literature. Measurement of S-100b in serum has been introduced into the discussion as an additional screening tool for intracerebral injuries because routine cranial computed tomography (CCT) of a large number of patients causes logistic difficulties, and the neurologic examination is often impaired by a high frequency of coincidental intoxication. The aim of our study was to determine the diagnostic value of measuring S-100b in the serum of MHT patients to identify risk groups. Additional validity should be aquired by a comparison with plasma levels of polymorphonuclear neutrophil (PMN) elastase an established general trauma marker. A series of 52 patients with MHT were included in the prospective study. At admission the patients underwent a routine CCT scan to detect intracerebral lesions, and blood samples were drawn to investigate circulating levels of S-100b and PMN elastase. For comparison, data for a positive control group of 10 severe head trauma patients (initial Glasgow Coma Scale score < 8) and for a negative control group with 20 healthy volunteers were obtained. The interval between MHT and admission to our hospital was 73.4 ± 47.0 minutes. The initial S-100b serum levels of MHT patients were 0.470 ± 0.099 ng/ml, those of the positive control group were 7.16 ± 3.77 ng/ml, and those of the negative control group were 0.05 ± 0.01 ng/ml. Relevant pathologic CCT scans were detected in 28.8% of MHT patients; one patient of that group was subjected to immediate surgical intervention (1.9%). At a cut-off point of 0.1 ng/ml, the sensitivity of positive S-100b levels reached 100% and the specificity 40.5%. Plasma levels of PMN elastase reached 60.52 ± 10.75 ng/ml in the MHT group, 66.4 ± 14.92 ng/ml in the severely head-injured group, and 23.26 ± 1.53 ng/ml in the negative control group. Serum levels of S-100b seem to be a highly sensitive but not very specific marker for isolated neurotrauma. Measurement of this parameter may be helpful as an additional screening tool to identify high risk groups in the cohort of MHT patients.     

Posttraumatic distress, alcohol disorders, and recurrent trauma across level 1 trauma centers

BACKGROUND: Injured survivors of individual and mass trauma receive their initial evaluation in acute care. Few investigations have comprehensively screened for posttraumatic stress disorder (PTSD) symptoms and related comorbidities across sites. METHODS: This investigation included 269 randomly selected injury survivors hospitalized at two level 1 trauma centers. All patients were screened for PTSD, depressive, and peritraumatic dissociative symptoms during their surgical inpatient admission. Prior traumatic life events and alcohol abuse/dependence also were assessed. RESULTS: In this study, 58% of the patients demonstrated high levels of immediate posttraumatic distress or alcohol abuse/dependence. Regression analyses identified greater prior trauma, female gender, nonwhite ethnicity, and site as significant independent predictors for high levels of posttraumatic distress. CONCLUSIONS: High levels of posttraumatic distress, recurrent trauma, and alcohol abuse/dependence were present in more than half of acute care inpatients. Early mental health screening and intervention procedures that target both PTSD and alcohol use should be developed for acute care settings.     

Posttraumatic immune modulation in chronic alcoholics is associated with multiple organ dysfunction syndrome.

BACKGROUND: Patients with chronic alcohol abuse constitute approximately 50% of trauma care patients, and these patients have a two- to fourfold increase in posttraumatic infectious complications. Cytokines such as interleukin-6 (IL-6) and interleukin-10 (IL-10) and the adhesion molecule soluble endothelial selectin (sE-selectin) have been found to play an important role in the initial inflammatory response to trauma and the development of early and late multiple organ dysfunction syndrome (MODS). The aim of this study was to compare the immune modulation and clinical relevance between chronic alcoholic and nonalcoholic patients following trauma. METHODS: Sixty-three patients (37 alcohol abusers, 26 nonalcoholics) were included in this prospective controlled study. IL-6, IL-10, and sE-selectin were determined on admission and on days 2, 4, and 7 following admission to the ICU. RESULTS: On admission to the ICU but not on the following days of the study period, plasma IL-6, IL-10, and sE-selectin were significantly elevated in chronic alcoholic patients compared with nonalcoholics. The incidence of MODS was significantly higher in chronic alcoholic patients (89% vs. 50%, p < 0.01), whereas the incidence of pneumonia (35% vs. 19%, p < 0.17) and sepsis (14% vs. 0%, p < 0.07) did not reach statistical significance. CONCLUSION: The significantly elevated levels of IL-6, IL-10, and sE-selectin in chronic alcoholic trauma patients on admission to the ICU could play an important role in the development of MODS in intensive care. In patients with high levels of inflammatory mediators, immune modulatory treatment before the development of MODS may be considered.     

Influence of Injury Pattern on Incidence and Severity of Posttraumatic Inflammatory Complications in Severely Injured Patients

Abstract Background: Severe trauma causes systemic inflammatory response syndrome (SIRS) which may lead to multiple organ dysfunction syndrome (MODS) or multiple organ failure (MOF). The aim of this study was to evaluate the influence of the injury pattern on the incidence and severity of SIRS, sepsis, MODS, and mortality. Methods: A total of 1,273 patients with an injury severity score (ISS) of ≥ 9 points and survival of more than 3 days were included in this retrospective study. Outcome parameters were various grades of SIRS, sepsis, MODS, and mortality. Results: Severe non-infectious SIRS occurred in 23%, sepsis in 14%, and severe MODS in 14% of the patients. Serious (abbreviated injury scale (AIS) ≥ 3 points) head injury and the ISS represented the most potent risk factors for severe SIRS. As estimated by multivariate logistic regression analysis, the presence of severe extremity and pelvic injuries, the ISS, and the male gender were found to be independent risk factors for sepsis. Severe injuries of the abdomen were associated with an increased risk for sepsis in the univariate analysis. Severe injuries to the head or abdomen, the ISS, and the male gender represented independent risk factors for the development of severe MODS. Regarding the late (> 3 days after trauma) hospital mortality, severe head injury, the ISS, and the patient’s age were independent risk factors. Conclusions: Head injury predominantly determines the incidence of non-infectious systemic inflammation, MOF, and late hospital mortality of patients with severe trauma. Skeletal or abdominal injuries represent relevant risk factors for septic complications. Thus, the incidence of posttraumatic, life-threatening inflammatory complications is related with certain injury patterns in addition to the gender and the severity of trauma.     

Association between injury pattern of patients with multiple injuries and circulating levels of soluble tumor necrosis factor receptors, interleukin-6 and interleukin-10, and polymorphonuclear neutrophil elastase

BACKGROUND: Our knowledge about the bidirectional interactions between brain and whole organism after trauma is still limited. It was the purpose of this prospective clinical study to determine the influence of severe head trauma (SHT) as well as trauma in different anatomic injury regions on posttraumatic inflammatory mediator levels from patients with multiple injuries. METHODS: Thirty-five healthy controls, 33 patients with an isolated SHT, 47 patients with multiple injuries without SHT, and 45 patients with both SHT and multiple injuries were studied. The posttraumatic plasma levels of soluble tumor necrosis factor receptors p55 and p75, interleukin (IL)-6, IL-10, and polymorphonuclear neutrophil (PMN) elastase were monitored using enzyme-linked immunosorbent assay technique. The influence of head injuries as well as thorax, abdomen, and extremity injuries on the mediator release from patients with multiple injuries was investigated by multivariate linear regression models. RESULTS: The soluble tumor necrosis factor receptor p55/p75 ratio was significantly elevated within 3 hours of trauma in all three injury groups and returned to reference ratios after 12 hours. The lowest increase was found in patients suffering from an isolated SHT. Lowest mediator levels in this patient population were also found for IL-6, IL-10, and PMN elastase during the first 36 hours after trauma. Additional injuries to the head, thorax, abdomen, and extremity modulated mediator levels to a different degree. No specific effect was found for SHT when compared with other injury groups. Thorax injuries caused the quickest rise in mediator levels, whereas abdominal injuries significantly increased PMN elastase levels 12 to 24 hours after trauma. CONCLUSION: Traumatic injuries cause the liberation of various mediators, without any specific association between anatomic injury pattern and the pattern of mediator release.     

Major injury induces increased production of interleukin-10 in human granulocyte fractions

Patients with severe trauma or polytrauma frequently acquire alterations in immune functions which are correlated to dysbalanced cytokine synthesis. In these settings the role of polymorphonuclear neutrophil granulocytes (PMN) as cytokine-producing cells is less well characterized. The immunosuppressive role of interleukin (IL)-10 is well known, and increased systemic IL-10 levels are related to the severity of injury and to posttraumatic complications. We determined concentrations of IL-10 in culture supernatants of 30 individual PMN fractions isolated from 18 severely traumatized patients (15 polytraumata, Injury Severity Score: 18–41, 3 severely burned patients) admitted to intensive care units. IL-10 was analyzed by ELISA (R&D Systems, Wiesbaden, Germany). PMN were isolated from EDTA-anticoagulated peripheral blood employing a one-step procedure based on a discontinuous double Ficoll gradient. The cells [1×10⁶/ml RPMI 1640 supplemented with 10% fetal calf serum and 25 mM N-(2-hydroxyethyl)-piperazine-N′-(2-ethanesulfonic acid] were stimulated with 0.05% heat-killed Staphylococcus aureus (Pansorbin, Calbiochem-Novabiochem, Bad Soden, Germany) for 24 h using cell culture conditions. Our results show that PMN fractions of traumatized patients produce significantly (P<0.008) higher amounts of IL-10 (354± 95 pg/ml, n = 30) than normal healthy donor cells (125± 95 pg/ml, n = 7). IL-10 release from PMN fractions exceeded the release from isolated patients' peripheral blood mononuclear cells induced by similar stimulation or by stimulation with toxic shock syndrome toxin-1 (10 ng) and concanavalin A (2 μg). Our results provide evidence that PMN fractions play an active role in the development of posttraumatic immunosuppression by autocrine or paracrine mechanisms, for example, by suppressing one's own antimicrobial activities or determining the development of T-cell responses via their ability to release IL-10. Received: 9 March 1998; in revised from: 3 August 1998 / Accepted: 1 September 1998     

Neutrophil priming for elastase release in adult blunt trauma patients

BACKGROUND: Elevated plasma elastase levels have been reported following major trauma and isolated femoral fracture. Reamed femoral nailing has been shown to further increase plasma elastase levels. The aim of this study was to investigate polymorphonuclear neutrophil (PMN) priming for degranulation following major trauma and isolated long-bone/pelvis fracture by assessing the ability of PMN to release elastase in vitro in response to a stimulus. METHODS: We further analyzed PMN surface expression of the integrins CD11b and CD18 as markers of PMN activation. Ten major trauma (Injury Severity Score>or=18) patients and 12 patients with isolated long-bone/pelvis fracture were included in the study. Patients in the isolated fracture group were further stratified into reamed nail and external-fixation groups following surgery. RESULTS: A significant increase in the capacity of PMN to release elastase was seen following major trauma, but not in isolated fracture patients. Surgery did not further alter PMN elastase release. CD11b and CD18 expression was essentially unaltered in all groups. CONCLUSIONS: PMN is primed for increased degranulation following major trauma but not following isolated long-bone/pelvis fracture. Accumulation of primed, hyperactive PMN into tissues can lead to severe tissue damage and thus multiple organ failure.     

Neutrophil activation after burn injury: contributions of the classic complement pathway and of endotoxin

We attempt to elucidate the mechanisms of neutrophil (PMN) activation after burn injury. We previously reported prolonged elevations of PMN cell surface complement (C) opsonin receptor levels after burn trauma with a corresponding period of depressed PMN chemotaxis to C5a, which suggests that the C product, C5a, was responsible for PMN activation. However, a lack of direct correlation of C activation with C receptor levels soon after injury raised the possibility of a second PMN-activating substance. We therefore investigated the effect of endotoxin (LPS) on the expression of the C receptors (CR1 and CR3) by normal human PMNs. Concentrations from 0 to 50 ng/ml of LPS 026:B6 caused a dose response increase in the PMN surface expression of CR1 and CR3 as assessed by monoclonal antibody binding and indirect immunofluorescence. The relative CR1-dependent fluorescence rose from a mean of 50 to 385 and CR3 from 50 to 300. Chelation by ethylenediaminetetra acetic acid (EDTA) did not influence this dose response, thus ruling out the possibility of C activation by LPS--an inference supported by the lack of complement activation observed with these concentrations of LPS in normal serum. A similar dose response was obtained in the absence of other cell types or serum, which implies a direct effect that mimicked that of C5a. To determine the mechanism of the later, prolonged C activation after burn injury, we next examined C activation products in 22 patients with burn injuries. Elevations of plasma C3a desArg were present and persisted for 50 days. Elevations were at maximum levels on days 9 through 13 postburn (mean +/- standard error of mean [SEM], 496 +/- 47 ng/ml versus normal 113 +/- 32; p less than 0.01). These were accompanied by elevations of C4a desArg (917 +/- 154 ng/ml versus normal 424 +/- 50; p less than 0.01), which are indicative of classic pathway activation. Finally, we examined PMN function, phagocytosis and percentage killing of Staphylococcus aureus, and found PMN function to be unaltered in the 22 patients. Thus PMN activation after burn injury appears to be caused by LPS soon after injury and by C5a later after injury and affects only selected PMN functions.     

Leukocyte activity in the microcirculation of the leg in patients with chronic venous disease

Purpose: It has been suggested that leukocyte trapping and activation in the microcirculation of the leg skin causes lipodermatosclerosis and ulceration in patients with chronic venous disease. Ambulatory venous hypertension is accepted as the physiologic factor that leads to ulceration. We investigated leukocyte endothelial adhesion in patients who were subjected to short-term venous hypertension.Methods: Two groups of patients with venous disease were studied: group 1, varicose veins with skin changes (n = 15); and group 2, varicose veins without skin changes (n = 15). Blood samples were taken from a foot vein before and after standing for 30 minutes to raise the venous pressure in the lower limb, and after lying supine again for 10 minutes. The samples were analyzed for leukocyte surface CD11b and L-selectin (CD62L) expression using a flow cytometer. Plasma-soluble L-selectin was also measured using an enzyme-linked immunosorbent assay.Results: In patients with skin changes, median neutrophil CD11b levels fell from 4.66 to 3.83 arbitrary units (p = 0.005, Wilcoxon) after 30 minutes of venous hypertension. Median monocyte CD11b levels fell from 7.65 to 5.8 arbitrary units (p = NS, Wilcoxon) after venous hypertension and then fell further to 5.43 arbitrary units (p = 0.02 vs baseline; Wilcoxon) when the venous hypertension was removed. Neutrophil and monocyte L-selectin levels also fell in response to venous hypertension, remaining low even after venous hypertension was removed. A similar pattern was seen in patients with uncomplicated varicose veins. There was a rise in soluble L-selectin in the plasma of both groups of patients after venous hypertension, reflecting leukocyte adhesion to endothelium. In the group of patients with skin changes the level of soluble L-selectin rose from 695 ng/ml to 836 ng/ml (p = 0.02, Wilcoxon), and in the group without skin changes the rise was from 700 ng/ml to 801 ng/ml (p = 0.02, Wilcoxon).Conclusion: Venous hypertension results in sequestration of the more activated population of neutrophils and monocytes in the microcirculation of the leg in patients with venous disease. These cells bind to the endothelium, releasing L-selectin, and do not emerge from the limb when venous hypertension is reversed. These findings do not differ between patients with varicose veins and those with skin changes. (J Vasc Surg 1997 26:265-73.)     

Released granulocytic elastase: an indicator of pathobiochemical alterations in septicemia after abdominal surgery

To discover the role of lysosomal enzyme release from polymorphonuclear (PMN) leukocytes during septicemia, plasma levels of PMN elastase were measured with a newly developed enzyme-linked immunosorbent assay for detection of the PMN elastase-alpha 1-proteinase inhibitor complex (E-alpha 1PI). Plasma samples from 41 patients were assayed continuously before and after major abdominal surgery. The patients were divided into a group without infection (group A) and two septicemia groups (survivors in group B and nonsurvivors in group C). The E-alpha 1PI levels of the 11 patients in group A without any signs of pre- or postoperative infection were in the normal range (a normal value of 86.5 +/- 25.5 ng/ml has been reported in 153 healthy subjects), except for a small increase to 208.8 +/- 25.6 ng/ml 12 hours after surgery. When septicemia was confirmed clinically in patients in groups B and C, the E-alpha 1PI levels rose on average to six times the norm in group B (649.9 +/- 116.3 ng/ml) and to more than 10 times the norm in group C (985.0 +/- 154.6 ng/ml). Peak values greater than 2,200 ng/ml could be measured in both groups. In patients in group B, the E-alpha 1PI levels returned to normal during recovery, while in those in group C they remained significantly elevated (560.5 +/- 174.7 ng/ml) until death. Correlations were demonstrated between the amount of elastase released into the circulation and the decrease in the activities of antithrombin III, coagulation factor XIII, and alpha 2-macroglobulin, as well as the increased C-reactive protein in plasma. We conclude that release of elastase and other lysosomal factors from PMN cells plays a major role in the pathobiochemical alterations during septicemia. In addition, significantly elevated E-alpha 1PI levels in the postoperative course seem to be a suitable indicator for onset and persistance of sepsis as well as of the severity of this disorder in patients after major surgery.     

A single dose of endotoxin activates neutrophils without activating complement

Both complement (C) and neutrophils (PMN) are activated in critically ill patients. To evaluate the role of endotoxin in this response, we studied C activation products and PMN cell surface receptors in seven normal subjects before and after endotoxin (USRef 20 U/kg) or saline solution administered on separate occasions. By 4 hours, with endotoxin only, all subjects had myalgia, headache, an increase in body temperature and heart rate, and leukocytosis that returned to normal by 24 hours. At the same time, PMN cell surface receptors for the complement opsonin C3b increased, as measured by indirect immunofluorescence, rising to 251 +/- 44% of baseline by 4 hours (p less than 0.01) and remaining elevated at 24 hours (237 +/- 16%, p less than 0.01). PMN receptors for iC3b increased to 308 +/- 49% of baseline by 4 hours (p less than 0.02) and returned to normal by 24 hours. There was no change in plasma of C3a desArg, C4a desArg, and C5a desArg (4 hours: mean C3a: 153.4 +/- 11.5 ng/ml versus 176.2 +/- 16.2 ng/ml for saline solution, p = ns; C4a: 159.6 +/- 32 ng/ml versus 151.4 +/- 21 ng/ml, p = ns; C5a: undetectable). To confirm the lack of C activation, we examined PMN chemotaxis (CTX) to C5a for any impairment caused by prior in vivo exposure to C5a. CTX to C5a was unaffected (4 hours: 109% +/- 22% of normal versus 114% +/- 10% for saline solution, p = ns). PMN CTX to formyl-methionyl-leucine-phenylalanine and PMN phagocytosis and killing of S. aureus were also unaffected by endotoxin. Thus, a single dose of endotoxin produced a subjective febrile illness and precipitated sustained PMN activation as indicated by increased PMN cell surface complement receptor number in the absence of C activation.     

Role of adenosine triphosphate (ATP) in trauma-induced and elective hypothermia

BACKGROUND: In trauma patients hypothermia is a frequent event. According to the literature the majority of trauma patients are presenting a core temperature of less than 34 degrees C at admission. In contrast to the benefit of hypothermia in elective surgery, clinical experience with hypothermia in trauma patients has identified hypothermia to be one major cause of severe posttraumatic complications. It was hypothetized that this diverse effect of hypothermia is related to depletion of high energy phosphates like adenosine-tri-phosphate (ATP) in trauma patients. To verify this hypothesis the relation of ATP plasma levels and hypothermia was examined in a clinical study. METHODS: Three different groups of patients were under study. The first group (group A, normothermic control group) included patients (n = 15) undergoing elective surgery of the lower limb with a mean operation time of 113 minutes. The second study group, hypothermic control (group B), comprised patients (n = 15) that were subjected to elective coronary artery bypass operation under hypothermia (31 degrees C for 48 minutes, mean total operation time being 205 minutes). The third study group (group C) included trauma patients (n = 23, mean ISS of 24.7). At the time of admission 10 patients presented a core temperature > or = 34 degrees C (group C1, mean ISS 25.2, mean TA 34.5 degrees C), 13 patients presented a TA < 34 degrees C (group C2, mean ISS 26.0, mean TA 32.9 degrees C). In both groups of surgical patients the ATP plasma level was measured preoperatively, at 2 hr, 4 hr and 24 hr postoperatively. In trauma patients this measurement was performed at admission and 24 hours later. Within the same schedule body core temperature was recorded and the clinical course was documented as well. RESULTS: Elective limb surgery in normothermic patients resulted only in a transient decrease in ATP plasma levels (preoperative: 87.8 mumol/dl, 4 hr postoperative: 52.0 mumol/dl). At 24 hours the ATP plasma level (62.6 +/- 10.0 mumol/dl) has increased towards baseline level. Elective hypothermia in patients subjected to coronary bypass also resulted only in a transient decrease in ATP plasma levels. During the operation period, including hypothermia, the ATP plasma level was comparable (50.4 mumol/dl) to group A and also returned back towards normal values at 24 hours (58.2 mumol/dl). All trauma patients revealed a significant low ATP plasma level at admission as compared to both control groups. Looking at subdivided groups the most significant drop in ATP plasma level (28.5 mumol/dl) was noted in patients presenting an initial core temperature < 34 degrees C and ISS > 30. Even 24 hours later the ATP level of this subgroup was significantly diminished despite a rise up to 44.4 mumol/dl. In contrast an only moderate drop in ATP plasma concentration (59.2 mmol/dl) was noted in the group of TA > or = 34 degrees C and ISS < 20. This group revealed almost normal values (68.3 mmol/dl) 24 hours after trauma. Beside hypothermia the metabolic state, reflected by the plasma lactate levels, significantly influenced the ATP plasma levels, as high lactate levels were paralleled by low ATP levels. Also the over all outcome was related to injury severity and hypothermia. CONCLUSION: Hypothermia in elective surgery, established by active cooling, preserves the ATP storage and maintains an aerobic metabolism, which both contribute to the beneficial effect of hypothermia in ischemia/reperfusion in cardiovascular surgery. However, in trauma patients hypothermia is caused by insufficient heat production due to utilization of ATP under anaerobic metabolic conditions. Low ATP plasma levels combined with hypothermia seem to be a predisposition for posttraumatic complications like organ failure.     

25% Albumin modulates adhesive interactions between neutrophils and the endothelium following shock/resuscitation

BACKGROUND: Polymorphonuclear neutrophil (PMN) sequestration in the lung is a hallmark of acute respiratory distress syndrome (ARDS). We have shown that 25% Albumin (A25) resuscitation attenuates lung injury after hemorrhagic shock and lipopolysaccharide (LPS) exposure by reducing lung leukosequestration. We hypothesize that this protective property is mediated by alteration of neutrophil-endothelial cell adhesive interactions. MATERIALS AND METHODS: A 2-hit rodent model of shock resuscitation was used. CD11b and L-selectin were measured using flow cytometry in rat and human neutrophils ex vivo. Intercellular adhesion molecule-1 (ICAM-1) levels were measured by Northern blot and immunohistochemistry. RESULTS: Resuscitation with A25 attenuated the increase in PMN CD11b expression in Ringer's lactate (RL) resuscitated animals at end resuscitation and at 4-hour post-LPS. While PMN L-selectin levels remained stable in RL treated animals, A25 resuscitation resulted in a significant decrease in surface L-selectin expression at 4-hour post-LPS. ICAM-1 lung endothelial cell mRNA, was increased in RL resuscitated animals, however reduced with A25 use by 51%. The LPS induced ICAM-1 endothelial cell protein expression was also prevented with A25 resuscitation. Antioxidant property of albumin was shown to play a critical role in altering CD11b expression. CONCLUSIONS: The A25 exerts its lung-protective activity at various levels including altering the interaction between neutrophils and endothelial cells via suppressed expression of adhesion molecules. These findings suggest a novel role for A25 as an anti-inflammatory agent in PMN-mediated diseases such as ARDS.     

Change of elastase and cathepsin G content in polymorphonuclear leukocytes during hemodialysis

Previous studies have demonstrated an increment of polymorphonuclear (PMN) elastase plasma levels during hemodialysis, suggesting release of this proteinase during dialysis treatment. In order to gain further evidence that proteinases are liberated from PMN leukocytes during dialysis both plasma levels of PMN elastase and the content of elastase and cathepsin G in neutrophils were determined during 3 hours of hemodialysis with cellulosic membranes (Cuprophan) in 10 patients. In blood smears, obtained at different times during dialysis, neutrophils were classified into 3 groups according to their proteinase content. Thus, group I neutrophils contained low, group II moderate, and group III leukocytes contained high amounts of both proteinases. With regard to their elastase content, prior to the onset of dialysis, 6% of the circulating PMN leukocytes were classified as fraction I, 58% as fraction II, and 36% as fraction III neutrophils. After 15 minutes of dialysis, at the nadir of leukopenia, all fractions of PMN leukocytes were significantly reduced (fraction I: -9%, fraction II: -60%, and fraction III: -83%) as compared to initial values. 30 minutes into hemodialysis, there was a significant increase in fraction I (+ 78%), whereas fraction II (-28%) and fraction III (-70%) remained diminished. At 180 times of hemodialysis the increment of fraction I neutrophils was even more pronounced (+ 187%), fraction II was also increased (+ 16%), and fraction III neutrophils had almost reached initial values. The cathepsin G content of PMN leukocytes displayed a rather similar pattern during dialysis. As to plasma levels of PMN elastase, there was a steady and significant increase from baseline values of 107.3 +/- 11.5 ng/ml up to 388.1 +/- 51.6 ng/ml after 3 hours of hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer

BACKGROUND: Degarelix is a gonadotropin-releasing hormone antagonist (GnRH receptor blocker) with immediate onset of action, suppressing gonadotropins, testosterone, and prostate-specific antigen (PSA) in prostate cancer. OBJECTIVE: To determine the efficacy and safety of initial doses of 200mg or 240mg of degarelix and thereafter monthly subcutaneous maintenance doses of 80mg, 120mg, or 160mg of degarelix for the treatment of prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The 1-yr study was of open-label, randomised design and involved 187 patients (range: 52-93 yr, median: 72 yr) with histologically confirmed adenocarcinoma of the prostate and a baseline PSA >2ng/ml. RESULTS AND LIMITATIONS: At baseline, median serum testosterone was 4.13ng/ml (range: P25-P75, 3.37-5.19ng/ml) and PSA was 27.6ng/ml (range: P25-P75, 11.9-55.0ng/ml). On day 3, 88% and 92% of patients in the groups to whom 200-mg and 240-mg initial doses of degarelix were administered, respectively, had testosterone levels 相似文献   

Early detection of increased tumour necrosis factor alpha (TNFalpha) and soluble TNF receptor protein plasma levels after trauma reveals associations with the clinical course

BACKGROUND: The inflammatory response after trauma includes tumour necrosis factor alpha (TNFalpha) as pro-inflammatory cytokine. Furthermore, both soluble TNF receptor proteins (sTNF-R1 and sTNF-R2) were described to influence the post-traumatic inflammatory response and organ dysfunction. METHOD: From 47 trauma patients, blood samples were obtained at the scene of accident, at hospital admission, after 4 h, 12 h, and 24 h, and daily until day 6. Plasma levels of TNFalpha, sTNFR1 and sTNF-R2 were measured by enzyme immunoassay (EIA) and analysed comparing clinical parameters such as injury scores (ISS, AIS), development of multiple organ dysfunction syndrome (MODS) and/or systemic inflammatory response syndrome (SIRS), and outcome. RESULTS: Significant changes were observed in a time-dependent manner: TNFalpha and soluble TNF receptor levels were elevated compared to values of healthy persons. At 4 h after trauma, TNFalpha and sTNF-R2 showed an increase from initial values, which continued during the entire observation period. Severe trauma led to enhanced sTNF-R1 levels on scene and on hospital admission. Development of SIRS along with elevated sTNF-R1 began on scene and was present on admission, with increased sTNF-R2 from day 1 to day 4. MODS (until day 6) was preceded by increased sTNF-R2 levels on admission and up to 4 h after trauma. Outcome was associated neither with TNFalpha nor with soluble TNF receptor levels. CONCLUSION: Thus, in trauma patients, early post-traumatic MODS and SIRS coincide with increased levels of TNFalpha and TNF receptor proteins, revealing different, time-dependent changes. Hence, detection of TNFalpha and soluble TNF receptor proteins after trauma should pay regard to the time point of sampling.     

Impact of clinically silent inflammation on male genital tract organs as reflected by biochemical markers in semen.

Three hundred eight-nine healthy, infertile patients were studied to determine the effects of inflammation on genital tract organs. Clinically silent inflammation was diagnosed by measuring polymorphonuclear granulocyte (PMN) elastase in semen. Seminal vesicle, prostate, and epididymis functions were assessed by measuring fructose, citric acid, and neutral alpha-glucosidase in semen. There was a significant relationship between high PMN elastase levels and low citric acid levels in semen; fructose and neutral alpha-glucosidase were not related to PMN elastase. Semen samples with increased PMN elastase levels (greater than 250 and greater than 1,000 ng/ml) showed a high incidence of pathologic citric acid levels (67% and 73%, respectively). These biochemical data indicate that the prostate is the main target in clinically silent male genital tract inflammation.     

Shed L-selectin (sCD62L) load in trauma patients

BACKGROUND: Low circulating plasma concentrations of the leukocyte adhesion molecule L-selectin (sCD62L) were found to be associated with an increased risk for subsequent lung failure and case fatality after severe trauma. The objective of this study was to determine the robustness of soluble L-selectin, correcting for a broad spectrum of physiological variables. METHODS: Patients with suspected multiple and/or trunk injuries were enrolled into this study over a 1-year period. Plasma samples were obtained on hospital presentation, and circulating soluble L-selectin was measured with a commercially available ELISA kit. Study records comprised all relevant clinical and laboratory data. Thirty-day survival rate, subsequent acute lung failure, and nosocomial pneumonia were defined as study endpoints. Statistical analysis was performed using multivariate logistic regression models. RESULTS: Seventy patients with a mean age of 35.51 years (range, 10-87 years) and a mean ISS score of 36.61 (95% CI, 31.08-42.14) entered the study. Eleven patients died, leading to an attributable mortality of 15.70%. L-Selectin levels did not differ between survivors and nonsurvivors. Five patients progressed to acute lung injury, whereas 11 patients developed hospital-acquired pneumonia. Lower L-selectin levels indicated patients at risk for lung injury with a relative odds estimated at 4.43 (P = 0.017). Statistical significance diminished in the multivariate model. In contrast, plasma concentrations of circulating sCD62L were significantly decreased in patients developing nosocomial pneumonia (P = 0.023), with a twofold increased relative odds (OR, 1.96; 95% CI, 0.51-7.50). No effect modification was observed by the included covariables. CONCLUSIONS: The results of this study highlight the independent predictive value of initially decreased soluble L-selectin levels for the identification of patients susceptible to subsequent respiratory complications after severe trauma.     

Impact of elective resection on plasma TIMP-1 levels in patients with colon cancer

OBJECTIVE: Pre- and post-operative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements. PATIENTS AND METHODS: Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all samples by a validated ELISA method. RESULTS: Geometric mean preoperative TIMP-1 level was 142 ng/ml (range 54-559 ng/ml) among CC patients compared with 106 ng/ml (range 64-167 ng/ml) among patients with nonmalignant diseases (P<0.0001). TIMP-1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant (P<0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP-1 levels at each time point. CONCLUSIONS: Major surgery has considerable impact on plasma TIMP-1 levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP-1 levels within 30 days postoperatively.     

Microvascular Transplantation of Adipose Tissue and Serum Level of Adipocyte Products

Microvascular transplantation of subcutaneous adipose tissue is an essential step in reconstructive surgery after breast carcinoma. Serum levels of adipose tissue products may serve as indicators for transplant function. This study aimed to determine serum leptin and tumor necrosis factor (TNF)-alpha plasma levels pre-, intra-, and postoperatively in 20 patients undergoing reconstructive breast surgery and in 7 women undergoing abdominoplasty operation. In the patients undergoing reconstructive breast surgery, the serum leptin levels decreased intraoperatively from 14.5 +/- 13.1 to 9.1 +/- 7.3 ng/ml, a decrease of 63%. An increase in serum leptin levels to 13.5 +/- 12.7 ng/ml (93% of the initial value) was found on postoperative day 1. This was paralleled by similar changes in the plasma levels of TNF-alpha (preoperatively, 20 +/- 7.3 pg/ml; intraoperatively, 17 +/- 11.4 pg/ml; postoperatively, 21 +/- 10.8 pg/ml). In the patients undergoing abdominoplasty, plasma leptin and TNF-alpha levels decreased intraoperatively (20% and 27%, respectively) and postoperatively (44% and 27%, respectively). The results of our pilot study indicate that a postoperative increase in the level of serum leptin after reconstructive breast surgery may be related to successful transplant function.