Biomedical subjects

M Jochum

Publications and source records attributed to M Jochum.

At least 19 recordsLinked to original sources

PubMed2005

Hemofiltration does not influence early S-100B serum levels in septic shock patients receiving stress doses of hydrocortisone or placebo.

BACKGROUND: The prognosis in patients with hyperdynamic septic shock correlates with the presence and the severity of septic encephalopathy. However, the neurological evaluation is considerably influenced by the use of analgesia sedation during mechanical ventilation. An early concentration peak of the neuroprotein S-100B in serum reflects both cellular damage at an increased permeability of the blood-brain-barrier and a delayed renal elimination. Thus, the objective of this study was to analyze the effect of continuous veno-venous hemofiltration (CVVH) on early S-100B serum levels in septic shock patients, who were treated with either stress doses of hydrocortisone or placebo. METHODS: Twenty-four consecutive patients, who met the ACCP / SCCM criteria for septic shock, were enrolled in this prospective, randomised, double-blind, single-center trial. The severity of illness at recruitment was graded using the APACHE II and SAPS II scoring systems; the MODS was described by the SOFA score. All patients were prospectively randomised to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. RESULTS: Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/ml (0.19-3.60) at study entry to 0.07 ng/ml (0.04 - 0.32) 6 days later without significant differences compared to the placebo group. Patients undergoing CVVH showed significantly higher S-100B serum values compared to patients without CVVH (p<0.001). However, initial median S-100B serum levels of the CVVH group even increased from 0.92 ng/ml (0.16 - 4.63) to 2.33 ng/ml (0.59 - 2.44) 30 hours after study entry, reaching data ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. CONCLUSION: Early S-100B serum levels in septic shock patients receiving either stress doses of hydrocortisone or placebo were not influenced by CVVH. For the first time, we observed a similar extent of S-100B serum increase in CVVH patients, who had significantly higher S-100B serum values compared to those without CVVH, as reported for out-of-hospital cardiac arrest or severe traumatic brain injury. Hypercortisolemia induced by the infusion of stress doses of hydrocortisone did not significantly reduce early S-100B serum concentrations with time.

Adult↗

PubMed2005

Hemofiltrastion does not influence early S-100B serum levels in septic shock patients receiving stress doses of hydrocortisone or placebo.

BACKGROUND: The prognosis in patients with hyperdynamic septic shock correlates with the presence and the severity of septic encephalopathy. However, the neurological evaluation is considerably influenced by the use of analgesia sedation during mechanical ventilation. An early concentration peak of the neuroprotein S-100B in serum reflects both cellular damage at an increased permeability of the blood-brain-barrier and a delayed renal elimination. Thus, the objective of this study was to analyze the effect of continuous veno-venous hemofiltration (CVVH) on early S-100B serum levels in septic shock patients, who were treated with either stress doses of hydrocortisone or placebo. METHODS: Twenty-four consecutive patients, who met the ACCP / SCCM criteria for septic shock, were enrolled in this prospective, randomised, double-blind, single-center trial. The severity of illness at recruitment was graded using the APACHE II and SAPS II scoring systems; the MODS was described by the SOFA score. All patients were prospectively randomised to receive either stress doses of hydrocortisone or placebo. Hydrocortisone was started in 12 patients with a loading dose of 100 mg and followed by a continuous infusion of 0.18 mg/kg/h for 6 days. RESULTS: Median S-100B serum levels of the hydrocortisone group decreased from 0.32 ng/ml (0.19-.60) at study entry to 0.07 ng/ml (0.04-0.32) 6 days later without significant differences compared to the placebo group. Patients undergoing CVVH showed significantly higher S-100B serum values compared to patients without CVVH (p>0.001). However, initial median S-100B serum levels of the CVVH group even increased from 0.92 ng/ml (0.16 - 4.63) to 2.33 ng/ml (0.59-2.44) 30 hours after study entry, reaching data ranges already known in patients with out-of-hospital cardiac arrest or severe traumatic brain injury. CONCLUSION: Early S-100B serum levels in septic shock patients receiving either stress doses of hydrocortisone or placebo were not influenced by CVVH. For the first time, we observed a similar extent of S-100B serum increase in CVVH patients, who had significantly higher S-100B serum values compared to those without CVVH, as reported for out-of-hospital cardiac arrest or severe traumatic brain injury. Hypercortisolemia induced by the infusion of stress doses of hydrocortisone did not significantly reduce early S-100B serum concentrations with time.

Adult↗

PubMed2004

[Identification of high-risk patients after minor craniocerebral trauma. Measurement of nerve tissue protein S 100].

The indication for an initial cranial computed tomography (CCT) in minor head trauma (MHT) patients remains the subject of discussion. The aim of this study was to investigate whether a newly developed, rapid test system (ELECSYS S100, Roche Diagnostics) might allow a diagnostically valid, reproducible measurement of S 100 in MHT patients. Blood samples were drawn from 75 MHT patients, a CCT scan was performed, and those with a post-traumatic intracranial lesion counted as CCT+. Results were compared to a healthy control group (n=17). Of the 75 patients included in the study, 14 were stratified as CCT+. The systemic concentration of S 100 in these CCT+ patients was significantly increased (0.31 microg/l) compared to the healthy control group (0.04 microg/l) as well as to the CCT-negative patients (0.08 microg/l). The ELECSYS S100 system allows a rapid, valid, and reproducible assessment of S 100B in patient serum and this concentration is significantly elevated in patients suffering from intracranial lesions as shown by initial CCT scan. Hence, this study is the basis for a multicenter trial currently underway to confirm the results of our pilot study.

Adult↗

PubMed2003

Initial RNA expression in human monocytes after multiple injury: a screening pilot study on potentially trauma-sensitive factors by using the microarray-technique.

BACKGROUND: Pathological affection of the immune system is one of the initiating mechanisms for the induction of multiple organ failure (MOF) in patients suffering from multiple injuries. Potential responsible intracellular mechanisms such as initial monocyte mRNA expression of specific mediators remain poorly studied, so far. Hence, we applied the microarray technique for screening of a wide variety of genes in circulating monocytes of multiple injured patients and compare the molecular results to the clinical course of the patients (MOF-score). METHODS: In our prospective pilot study 6 patients were enclosed presenting with blunt multiple injuries (Injury Severity Score 16 to 57 points). Monocytes were isolated out of sequentially drawn samples (6, 12, 24 and 48 hours after trauma) using magnetic cell sorting (CD14) and a human microarray system was used (Atlas stress 1.2, Clontech, 1176 genes). Alterations in the sequential samples were identified by calculating ratios to baseline levels on admission and cluster analysis was performed (Spotfire Decision). RESULTS: Only 86 (ca.5%) genes displayed an obvious signal. The house-keeping genes clustered well together in all patients in contrast to a substantial inter-individual variability of the other signal giving genes. No mediator burst of the classical pro- or anti-inflammatory cascade were detected. CONCLUSION: We demonstrate for the first time a screening analysis of mRNA expression patterns in circulating monocytes of multiple injured patients indicating that only very few genes appeared to be influenced by the traumatic event. So far, no correlation to the severity of trauma or MOF could be detected.

Adult↗

PubMed2003

Serum S-100B protein levels in young amateur soccer players after controlled heading and normal exercise.

BACKGROUND: Repeated impacts by heading might lead to significant head injuries in soccer players comparable to those of patients with accidental minor traumatic brain injury (TBI). The neuroprotein S-100B released into the circulation is suggested to be a reliable marker indicating brain damage. The objective was to evaluate the neuroprotein S-100B serum levels in young amateur soccer players early after controlled heading compared to early measurements after normal exercise as well as in other patients after minor TBI. MATERIAL AND METHODS: Sixty-one male amateur soccer players (median age 15.3 years) performed controlled heading aimed at the forehead for 55 minutes. Data were compared to 58 male amateur soccer players (15.9 years) performing 61 minutes of normal exercise training without head contact and 81 young male patients early after TBI who underwent computed tomography (CCT) for detection of intracranial lesions. First venous blood samples were drawn before the training sessions, second and third samples 60 and 360 minutes after heading or 64 and 355 minutes after exercise, respectively, 65 and 366 minutes after TBI. RESULTS: Median S-100B serum levels of the heading group only slightly increased from 0.15 ng/ml to 0.18 ng/ml 60 minutes after end of training. Within 360 minutes S-100B values decreased again to 0.15 ng/ml reaching the initial values. S-100B serum values of the exercise group showed a similar transient increase exhibiting significant lower levels before exercise (0.10 ng/ml) as well as 64 minutes (0.11 ng/ml) and 355 minutes after exercise (0.09 ng/ml) compared to the heading group. According to age stratification in the heading group, starting median S-100B levels were significantly higher in subjects with 12-13 years (0.22 ng/ml) and 14-15 years (0.17 ng/ml) compared to those with 16-17 years of age (0.06 ng/ml). None of the subcollectives did reach median S-100B levels of the CCT+ group (n = 20) at admission (0.62 ng/ml) or 366 minutes later (0.32 ng/ml), which were significantly elevated compared to those of the CCT group (n = 61) at admission (0.10 ng/ml) or 370 minutes later (0.08 ng/ml). CONCLUSIONS: Controlled repetitive heading in young amateur soccer players leads to a transient increase between 60 to 360 min after training, but does not appear to evoke a longer lasting S-100B release into serum indicating cellular brain damage. After heading S-100B levels are significantly elevated compared to normal exercise. Although soccer players with 12-13 years and 14-15 years revealed significantly higher S-100B values than with 16-17 years of age, the transient increase is independent of the age-related starting values. However, since brain damage due to abrupt heading a ball of high speed or accidental trauma during regular soccer games cannot be excluded, S-100B measurements in soccer players are initiated during video-controlled soccer games.

Adolescent↗

PubMed2003

Elevated expression of polymorphonuclear leukocyte elastase in breast cancer tissue is associated with tamoxifen failure in patients with advanced disease.

Besides a variety of other proteases, polymorphonuclear leukocyte elastase (PMN-E) is also suggested to play a role in the processes of tumour cell invasion and metastasis. Yet, there is only limited data available on the relation between the tumour level of PMN-E and prognosis in patients with primary breast cancer, and no published information exists on its relation with the efficacy of response to systemic therapy in patients with advanced breast cancer. In the present study, we have measured with enzyme-linked immunosorbent assay the levels of total PMN-E in cytosolic extracts of 463 primary breast tumours, and have correlated their levels with the rate and duration of response on first-line tamoxifen therapy (387 patients) or chemotherapy (76 patients) in patients with locally advanced and/or distant metastatic breast cancer. Furthermore, the probabilities of progression-free survival and postrelapse survival were studied in relation to the tumour levels of PMN-E. Our results show that in logistic regression analysis for response to tamoxifen treatment in patients with advanced disease, high PMN-E tumour levels were associated with a poor rate of response compared with those with low PMN-E levels (odds ratio: OR, 0.40; 95% CI, 0.22-0.73; P=0.003). After correction for the contribution of the traditional predictive factors in multivariate analysis, the tumour PMN-E status was an independent predictor of response (P=0.01). Furthermore, a high tumour PMN-E level was related with a poor progression-free survival (P<0.001) and postrelapse survival (P=0.002) in a time-dependent analysis. In contrast, the tumour level of PMN-E was not significantly related with the efficacy of response to first-line chemotherapy in patients with advanced breast cancer. Our present results suggest that PMN-E is an independent predictive marker for the efficacy of tamoxifen treatment in patients with advanced breast cancer.

Adult↗

PubMed2002

Rapid identification of high-risk patients after minor head trauma (MHT) by assessment of S-100B: ascertainment of a cut-off level.

BACKGROUND: Elevated blood S-100B levels were described by several authors for reliable identification of patients with intracerebral complications after minor head trauma (MHT). Yet, test systems used so far require more than 3 hours processing period which is too long to enable immediate further diagnostic or therapeutic consequences. Therefore we validate a new rapid test version for S-100B measurements and established an effective cut-off level to identify high risk patients. METHODS: 104 patients suffering from MHT were enrolled. After taking blood samples S-100B values were achieved by the long-term and rapid (40 min processing time) test system, respectively, and compared using linear regression analysis. For determination of an effective cut-off level receiver operating characteristics curves were calculated in accordance with cranial computed tomography findings. RESULTS: S-100B concentrations correlated significantly using both test systems. A cut-off level of 0.18ng/ml was calculated in plasma samples. CONCLUSIONS: S-100B concentrations above the cut-off level measured within 40 min after blood sampling allows safe identification and immediate treatment of intracerebral lesions (e.g. epidural and subdural hematoma, subarachnoid hemorrhage, diffuse brain edema etc.) in MHT patients.

Blood Chemical Analysis↗

PubMed2002

Systemic regulation of distraction osteogenesis: a cascade of biochemical factors.

This study investigates the systemic biochemical regulation of fracture healing in distraction osteogenesis compared with rigid osteotomy in a prospective in vivo study in humans. To further clarify the influence of mechanical strain on the regulation of bone formation, bone growth factors (insulin-like growth factor [IGF] I, IGF binding protein [IGFBP] 3, transforming growth factor [TGF] beta1, and basic FGF [bFGF]), bone matrix degrading enzymes (matrix-metalloproteinases [MMPs] 1, 2, and 3), human growth hormone (hGH), and bone formation markers (ALP, bone-specific ALP [BAP], and osteocalcin [OC]) have been analyzed in serum samples from 10 patients in each group pre- and postoperatively. In the distraction group, a significant postoperative increase in MMP-1, bFGF, ALP, and BAP could be observed during the lengthening and the consolidation period when compared with the baseline levels. Osteotomy fracture healing without the traction stimulus failed to induce a corresponding increase in these factors. In addition, comparison of both groups revealed a significantly higher increase in TGF-beta1, IGF-I, IGFBP-3, and hGH in the lengthening group during the distraction period, indicating key regulatory functions in mechanotransduction. The time courses of changes in MMP-1, bone growth factors (TGF-beta1 and bFGF), and hGH, respectively, correlated significantly during the lengthening phase, indicating common regulatory pathways for these factors in distraction osteogenesis. Significant correlation between the osteoblastic marker BAP, TGF-beta1, and bFGF suggests strain-activated osteoblastic cells as a major source of systemically increased bone growth factors during callus distraction. The systemic increase in bFGF and MMP-1 might reflect an increased local stimulation of angiogenesis during distraction osteogenesis.

Adult↗

PubMed2001

S-100b, sE-selectin, and sP-selectin for evaluation of hypoxic brain damage in patients after cardiopulmonary resuscitation: pilot study.

S-100b is thought to be a screening marker of hypoxic brain damage in patients with cardiac arrest. However, the time-dependent occurrence and relevance of increased S-100b serum levels in out-of-hospital patients with cardiopulmonary resuscitation (CPR) is still discussed. The purpose of our study was to evaluate the diagnostic utility of S-100b measurements in comparison to that of adhesion molecules sE-selectin and sP-selectin in patients with CPR. Sixteen out-of-hospital patients (median age 69.6 years; range 59.2-82.2 years) suffering from cardiac arrest due to ventricular fibrillation, asystole, or electromechanical dissociation were recruited prospectively. Blood samples were drawn on scene after the return of spontaneous circulation (ROSC) and 12 hours after successful CPR. The reference group consisted of 10 patients with isolated severe head trauma (SHT) (Glasgow Coma Score </ or =8), and the control group comprised 20 healthy volunteers. Serum concentrations of S-100b, determined by immunoluminometric assay, were compared with serum levels of sE-selectin and sP-selectin measured by an enzyme-linked immunosorbent assay and correlated with the patients' survival. In the CPR group, S-100b serum levels (2.37 ng/ml; 1.37-4.09 ng/ml) at study entry (11.6 minutes after arriving on scene) did not significantly differ from those of SHT patients (2.88 ng/ml; 1.78-8.81 ng/ml). Both groups showed significant differences from the healthy controls (0.04 ng/ml; 0.01-0.82 ng/ml). At 12 hours after CPR the serum levels had decreased to 0.41 ng/ml (0.24-0.51 ng/ml) but continued to be significantly elevated compared to that of the control group. sE-selectin values in serum increased from 56.00 ng/ml (38.50-85.50 ng/ml) on scene to 79.00 ng/ml (52.00-127.00 ng/ml) after 12 hours (p < 0.05). The first measurements differed significantly from serum levels of the control group (22.50 ng/ml; 14.00-34.00 ng/ml) and from those of the SHT group (45.00 ng/ml; 39.00-63.75 ng/ml). At 12 hours after study entry the sE-selectin values were not significantly different from those of the SHT group (51.50 ng/ml; 39.00-95.88 ng/ml). sP-selectin serum levels increased slightly from 199.50 ng/ml (184.25-227.25 ng/ml) to 247.00 ng/ml (206.50-354.75 ng/ml). First and second measurements did not reveal any significant differences in either the SHT group or the healthy controls. When correlated with survival, S-100b measurements exhibited constantly high serum levels for patients, decreasing within the first 24 hours, whereas they decreased significantly in patients with longer survival. sP-selectin values on scene slightly increased in cases of survivals less than 24 hours after CPR. sE-selectin serum levels always remained within normal levels and revealed no significance later on. In contrast to the endothelium-derived adhesion molecules sE-selectin and sP-selectin, comparison of measurements of specific neuroprotein S-100b early after cardiac arrest and 12 hours later seem to provide an indication of the severity of hypoxic brain damage and the prognosis after CPR. Further investigations are required to better understand the CPR-related mechanisms of blood-brain barrier damage.

Aged↗

PubMed2001

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.

Autoantigens↗

PubMed2001

Early cellular brain damage and systemic inflammatory response after cardiopulmonary resuscitation or isolated severe head trauma: a comparative pilot study on common pathomechanisms.

Severe neurological deficits are common characteristics of patients surviving cardiopulmonary resuscitation (CPR) or isolated severe head trauma (SHT). For comparative evaluation of underlying pathomechanisms, 22 patients with out-of-hospital cardiac arrest and successful CPR as well as 10 patients with SHT were included in our prospective study. Circulating S-100B was determined as an indicator of cellular brain damage. Interleukin-8 (IL-8), soluble E-selectin (sE-selectin) and polymorphonuclear (PMN-) elastase were measured as markers of systemic inflammation following whole body ischaemia and reperfusion injury. Venous blood samples were drawn on scene (median time 11.0 min after starting basic life support) and in the intensive care unit (median time 12.5 h thereafter) in CPR patients and at admission to hospital (median time 43.8 min after trauma) and approx. 12 h later in SHT patients. Biochemical parameters in these samples were compared with specimens taken from 20 healthy volunteers. Initial median S-100B levels of the CPR and SHT patients were both significantly increased compared with the controls. Twelve hours later, significant falls in S-100B revealed no differences between the two patient groups, but did not reach control values. Median IL-8 and sE-selectin levels entry to the study were elevated in both patient groups compared with controls and showed further rises within the following 12 h. Finally, increased initial median levels of PMN-elastase revealed significant differences between the patient groups and between patients and controls. Twelve hours later, median PMN-elastase values were equally elevated in the CPR and SHT subjects. Our preliminary data suggest similar pathomechanisms occurring after both CPR and SHT. Both clinical entities seem to be associated with early transient cellular brain damage as shown by prolonged rapidly increasing and subsequent fall in S-100B serum levels. In contrast, the prolonged elevation of circulating IL-8, sE-selectin and PMN-elastase may indicate a very similar systemic inflammatory response by endothelial cells and neutrophils initiated by ischaemia and reperfusion injury in both conditions. Further studies should be carried out to determine the cause and the prognostic value of these biochemical parameters in relation to long-term neurological outcome.

Aged↗

PubMed2001

Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates.

OBJECTIVE: To determine if prophylactic administration of C1-esterase-inhibitor would have a beneficial effect on postoperative weight gain and the inflammatory response in neonates undergoing cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Randomized, double-blinded study. SETTING: University-affiliated heart center. PARTICIPANTS: Twenty-four neonates with transposition of the great arteries. INTERVENTIONS: In group inhibitor (INH) patients (n = 12), 100 IU/kg of C1-esterase-inhibitor (Berinert) was given 30 minutes before CPB. In group placebo (P) patients (n = 12), placebo was administered instead. Interleukin (IL)-6, C3a anaphylatoxin, C1 activity, prekallikrein, Hageman factor, D-dimers, and clinical parameters were measured 6 times perioperatively. MEASUREMENTS AND MAIN RESULTS: All 24 patients had an uneventful clinical course. Mean arterial pressure and pulmonary oxygenation after CPB were superior in group INH patients. The weight gain on postoperative days 1 to 4 was significantly less in group INH patients compared with group P (55 +/- 59 g vs. 340 +/- 121 g, day 1). The concentration of IL-6 (76 +/- 17 pg/mL vs. 262 +/- 95 pg/mL during CPB) was significantly lower in group INH patients compared with group P patients. In contrast, no influence on C3a anaphylatoxin and coagulation factors was found. CONCLUSION: Prophylactic application of C1-esterase-inhibitor in neonates undergoing arterial switch operations produces less inflammatory response compared with placebo. This difference may have contributed to improved clinical parameters, including less weight gain postoperatively.

Capillary Leak Syndrome↗

PubMed2001

Is perioperative plasma aprotinin concentration more predictable and constant after a weight-related dose regimen?

UNLABELLED: To determine whether a weight-related dose had advantages over a fixed, large-dose regimen, we measured plasma concentrations of aprotinin by using an enzyme-linked immunosorbent assay method at set time points in 30 patients having heart surgery with cardiopulmonary bypass. A weight-related dose comprising a preincision bolus injection of 40,000 kallikrein-inhibiting units (KIU)/kg (5.6 mg/kg) with the same amount given in the oxygenator prime was compared with a large-dose regimen of 2 x 10(6) KIU (280 mg) preincision bolus and addition to prime, together with an infusion of 500,000 KIU/h (70 mg/h). Peak plasma concentration in the Weight-Related group was less variable than with the fixed-dose regimen. Forty percent of patients allocated to the fixed-dose regimen had an aprotinin concentration of more than 400 KIU/mL, compared with none in the Weight-Related group; this suggests a relative overdosing in the early surgical period in the Fixed-Dose group. There was great individual variability between patients in the time-concentration curves for aprotinin, with no difference between the two regimens. The weight-related dose regimen benefited by not requiring an intraoperative infusion while achieving the same plasma concentrations of aprotinin. IMPLICATIONS: Peak plasma concentrations of aprotinin were less variable with a weight-related dose schedule. This has implications for safety with regard to control of anticoagulation and cost in patients with small body mass. Plasma concentrations varied greatly with time between patients. This observation has implications for determining an optimal dose on the basis of aprotinin's currently known mechanisms of action.

Adult↗

PubMed2001

Determination of plasma aprotinin levels by functional and immunologic assays.

We compared a functional (amidolytic) and an enzyme-linked immunosorbent assay (ELISA) method for determining aprotinin concentration in 82 plasma samples obtained from patients undergoing cardiac surgery with aprotinin therapy. There was good correlation between methods (r = 0.87); however, aprotinin measurements by chromogenic assay were significantly higher than by ELISA [234 +/- 104 kallikrein inhibitory units (KIU)/ml versus 155 +/- 88 KIU/ml; P = 0.0001]. This appeared to be attributable to differences in the potency of the material used to standardize the assays. When results were corrected to allow for potency of the standard, there was no significant difference between chromogenic and ELISA methods (234 +/- 104 KIU/ml versus 240 +/- 137 KIU/ ml), although the ELISA results tended to be higher in some samples. These data suggest that aprotinin concentrations measured by these methods cannot be used interchangeably, and care must be taken when interpreting data from studies measuring aprotinin.

Aprotinin↗

PubMed2001

The effect of trauma on neutrophil L-selectin expression and sL-selectin serum levels.

Among identified adhesion molecules, the L-selectin on neutrophils enables the first step of leukocyte adherence to activated endothelial cells. To allow firm adhesion of neutrophils, L-selectin is then split off the cell membrane. It was hypothetized that an increase of the constitutively high serum level of soluble L-selectin may indicate an ongoing pathological neutrophil sequestration to the endothelial cells associated with activation and injury of the cells. To evaluate this hypothesis, sL-selectin serum levels and neutrophil L-selectin expression of healthy volunteers (group A, n = 15), as well as of surgical patients, were investigated. Group B (n = 26) included patients subjected to elective limb surgery (mean operation time, 122 min), and group C (n = 45) comprised trauma patients. sL-selectin serum levels were measured daily over a 14-day period. Neutrophil L-selectin expression was evaluated by FACS analysis using the humanized anti-L-selectin antibody HuDreg 55 over a period of 3 days at minimum in both experimental groups. The binding of sL-selectin to endothelial cells was also examined in vitro. Elective limb surgery resulted in lower pre- and post-operative sL-selectin plasma levels (800-1,000 ng/mL) compared to healthy volunteers (1,100-1,200 ng/mL) with insignificant changes throughout the study period. Trauma patients revealed even lower sL-selectin levels (400-600 ng/mL). When these patients were discriminated by the multiple organ dysfunction (MOD) score of Moore in +MOD (n = 9, ISS = 31.7) and -MOD (n = 36, ISS = 25.0), a significant difference became evident. In +MOD patients sL-selectin levels remained on a low basis of 350 ng/mL, whereas in -MOD patients the initial low sL-selectin level subsequently rose to 800 ng/mL, similar to that of elective surgery patients. FACS analysis revealed a significant drop in neutrophil L-selectin expression 24 h after trauma compared to normal. Also, +MOD and -MOD patients were significantly discriminated by the L-selectin expression at this time. The in vitro studies revealed evidence for binding of sL-selectin to endothelial cells independently on the presence of neutrophils. According to our data, increasing severity of the post-operative/posttraumatic course is associated with decreasing sL-selectin serum levels and also reduced neutrophil L-selectin expression. In view of the in vitro results, this probably indicates competitive enhanced binding of sL-selectin to endothelial cells, thus masking the elevated activation of neutrophils and their ability for endothelial adherence.

Adolescent↗

PubMed2001

Endotoxemia and cytokine generation in cardiac surgery in relation to flow mode and duration of cardiopulmonary bypass.

We investigated whether pulsatile flow in cardiopulmonary bypass (CPB), which has been shown to improve intestinal perfusion, reduces endotoxin translocation from the gut and, in consequence, decreases cytokine generation. The study population consisted of 48 adult patients who underwent elective CPB surgery. Pulsatile flow was used during aortic cross-clamping in 24 patients and nonpulsatile flow in 24 patients. Plasma endotoxin concentration increased in all patients during CPB. Significantly (P < 0.05) lower peak levels of 8.25 +/- 1.17 (SEM) pg/mL were reached 30 min after CPB in patients with pulsatile flow in contrast to 11.26 +/- 1.42 pg/mL in patients with nonpulsatile flow. The extent of endotoxemia was not related to the duration of CPB. Following the increase of plasma endotoxin, the concentrations of IL-6 and IL-8 increased with delay of approximately 1 h. The peak levels of these cytokines corresponded significantly (P < 0.005 and P < 0.01, respectively) with duration of CPB, but not with flow mode. Thus, in patients with CPB of more than 97 min (median), IL-6 reached a peak of 335.5 +/- 48.87 pg/mL and IL-8 of 64.86 +/- 24.79 pg/mL in contrast to 210.9 +/- 18.45 pg/mL and 21.2 +/- 10.19 pg/mL, respectively, with bypass times of less than 97 min. The degree of endotoxemia in CPB mainly depends on the quality of tissue perfusion. Cytokine generation, however, is not triggered exclusively by endotoxin, but rather by the trauma of CPB and surgery.

Aged↗

PubMed2001

Elevated serum levels of S-100B reflect the extent of brain injury in alcohol intoxicated patients after mild head trauma.

Elevated systemic levels of S-100B are proposed as a potential indicator of brain damage in identifying high-risk patients after mild head trauma (MHT). Although incidence of alcohol intoxication is high in these patients, the influence of alcohol intoxication on S-100B levels is unclear. Therefore, the aim of our study was to investigate serum concentrations of S-100B in intoxicated (group 1) and sober (group 2) patients after MHT in comparison with those of mild (group 3) or severely intoxicated (group 4) individuals without trauma. S-100B was significantly increased in MHT patients exhibiting posttraumatic lesions in initial cranial computed tomography scan. Alcohol intoxication did not elevate S-100B levels in group 3 or 4 subjects. Our data indicate for the first time that alcohol intoxication does not influence the diagnostic value of S-100B measurements in patients after MHT.

Alcohol Drinking↗

PubMed2001

Kinins 1925-2000.

Explore the source record for details and available documents.

History, 20th Century↗