采用HA130型树脂灌流器血液灌流对维持性血液透析患者微炎症的影响

背景：研究发现维持性血液透析的尿毒症患者体内存在“微炎症状态”。 目的：观察采用HA130型树脂灌流器行血液灌流对维持性血液透析患者微炎症的影响。 方法：选取维持性血液透析治疗的尿毒症患者60例,随机分为2组,灌流组采用HA130型树脂灌流器串联血液透析器进行血液灌流加血液透析治疗;透析组行单纯血液透析治疗。采集治疗前后两组患者的血清,检测高敏C-反应蛋白、肿瘤坏死因子α和白细胞介素6水平。 结果与结论：灌流组血清高敏C-反应蛋白、白细胞介素6和肿瘤坏死因子α水平治疗后较治疗前显著降低(P < 0.05);透析组治疗后上述指标较治疗前略升高,差异无显著性意义。提示血液灌流可以降低维持性血液透析患者血清高敏C-反应蛋白、白细胞介素6和肿瘤坏死因子α水平,有利于减轻其微炎症反应。     

Relationship between effect of polymyxin B-immobilized fiber and high-mobility group box-1 protein in septic shock patients

Direct hemoperfusion (DHP) using a polymyxin B (PMX)-immobilized fiber column has been used for treatment of endotoxemia-induced septic shock in Japan since 1994 and is now an accepted therapy for reducing serum endotoxin levels. Although a reduction in inflammatory cytokines has been reported, the detailed mechanism of DHP-PMX is not known. We investigated the high-mobility group box-1 (HMGB-1) level in septic shock patients treated with DHP-PMX. Subjects (n = 20) were separated into two group: those whose systolic blood pressure increased to more than 30 mm Hg immediately after DHP-PMX (effective [E] group: nine cases) and those whose systolic blood pressure did not increase to more than 30 mm Hg (noneffective [N-E] group: 11 cases). The interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were measured in each group. The Pao2/Fio2 ratio and the Sepsis-Related Organ Failure Assessment (SOFA) score were also evaluated. Pretreatment interleukin-6, plasminogen activator inhibitor-1, and HMGB-1 levels were similar in the E and N-E groups, but mortality rate was significantly higher in the N-E group. Furthermore, posttreatment SOFA score was significantly lower in the E group. In the E group, only the HMGB-1 levels improved significantly after DHP-PMX. Present data suggest that the circulation dynamics of septic shock patients can be improved by reducing HMGB-1 levels by using DHP-PMX.     

Coronary angiographic findings in patients with clinical unstable angina according to cardiac troponin I and T concentrations in serum

CONTEXT: Elevated cardiac troponin levels have been reported to identify unstable angina patients at high risk. OBJECTIVE: To examine the relation of cardiac troponin I (cTnI) and cardiac troponin T (cTnT) levels to findings of coronary angiography in these patients. METHODS: Samples for troponin estimation were taken every 4 hours throughout the first 48 hours after admission before angiography in 34 patients with primary unstable angina. Patients were considered to be troponin positive if the marker was increased (>0.04 microg/L for cTnT and >0.03 microg/L for cTnI) in at least one sample collected. RESULTS: An increased troponin (I or T) concentration was documented in 14 patients (41.2%). Twelve patients (35.3%) had elevations of both markers, whereas the remaining 2 patients had elevations of cTnI or cTnT alone. Patients with or without increased troponin levels did not differ with respect to degree of coronary disease at angiography. However, patients with elevated troponin concentrations had more complex lesion characteristics. In 69% of patients with increased cTnI levels and in 77% of patients with increased cTnT levels, type B2 or C lesions were documented with presence of ulcerated plaques and thrombus formation. In contrast, only 23% of the patients with elevated cTnI or cTnT levels had type A lesions compared with 71% of patients with negative troponin concentrations. CONCLUSIONS: Patients with unstable angina who have significant release of cTnI and/or cTnT have evidence of more complex lesions on coronary angiography, supporting the hypothesis that both troponins might be used without distinction as surrogate markers for microembolization from thrombus formation on a disrupted plaque.     

Effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter after polymyxin B-immobilized fiber column therapy of septic shock

Septic shock is a condition associated with diffuse coagulopathy and multiple organ failure, and frequently ends in death. Direct hemoperfusion using a polymyxin B-immobilized fiber column (DHP-PMX) was first developed in Japan in 1994 and has since been used for the treatment of septic shock. On the other hand, the effectiveness of continuous hemodiafiltration using a polymethylmethacrylate membrane hemofilter (PMMA- CHDF) for critically ill patients has also been reported. We treated 27 septic shock patients by DHP-PMX. The patients, except for the nine in whom CHDF was not performed after DHP-PMX, were divided into two groups: namely, a group in which PMMA-CHDF therapy was added after DHP-PMX (11 cases), and a group in which continuous hemodiafiltration using a polyacrylonitrile membrane hemofilter (PAN-CHDF) therapy was added after DHP-PMX (7 cases). The outcomes in the two groups were compared. The average Acute Physiology and Chronic Health Evaluation (APACHE) II score and the average sepsis-related organ failure assessment (SOFA) score were not significantly different between the two groups. The PMMA-CHDF group showed significantly better outcomes, with significant improvements of the serum PAI-1, protein C, IL-6 and N-arachidonoylethanolamine (AEA) levels. We conclude that PMMA-CHDF may be more effective than PAN-CHDF in the management of septic shock.     

Effectiveness of early start of direct hemoperfusion with polymyxin B-immobilized fiber columns judging from stabilization in circulatory dynamics in surgical treatment patients

Background:

Septic shock remains a major cause of multiple organ failure and is associated with a high mortality rate. In 1994, direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo Japan) was developed in Japan and has since been used for the treatment of septic shock arising from endotoxemia.

Materials and Method:

We treated 36 patients with septic shock using direct hemoperfusion with PMX. The patients were analyzed in two groups based on whether they had undergone surgery prior to DHP-PMX treatment (surgical group: surgical treatment before DHP-PMX, medical group: no surgical treatment). In surgical group, DHP-PMX was started within three hours after the surgical treatment. Various factors were measured before and after DHP-PMX.

Results:

The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 27.4 ± 8.8, and the mean sepsis-related organ failure assessment (SOFA) score was 11.8 ± 4.9 before DHP-PMX. The SOFA score was significantly higher (P = 0.0091) and the PaO2/FiO2 ratio (P/F ratio) was significantly lower (P = 0.0037) in medical group than in surgical group prior to DHP-PMX. A chi-square test showed that the survival rate in surgical group was significantly better than in medical group (P = 0.0027). The survival rate of surgical group (84.2%) was judged to be very good because the predicated survival rate based on the APACHE II score (25.0) was only 46.5%. On the other hand, the survival rate of medical group (35.3%) was almost equal to that predicted by the APACHE II score (30.6; predicted survival rate, 27.4%).

Conclusion:

The results of this study suggest the utility of early DHP-PMX in surgical group.     

Clinical responses and improvement of some laboratory parameters following polymyxin B-immobilized fiber treatment in septic shock

Direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo, Japan) was first developed in 1994 and has since been used for the treatment of septic shock. Positive clinical data, such as an increase in systolic blood pressure (SBP) and an improved Pao2/Fio2 ratio, have also been reported. We treated 27 septic shock patients using DHP-PMX. The patients were separated into two groups for analysis: those whose Pao2/Fio2 ratio increased after DHP-PMX (9 cases) and those whose Pao2/Fio2 ratio did not increase after DHP-PMX (18 cases). The patients were also separated into two other groups for analysis: those whose SBP increased by more than 30 mm Hg immediately after DHP-PMX (15 cases) and those whose SBP did not increase by more than 30 mm Hg after DHP-PMX (12 cases). The Pao2/Fio2 ratio increased significantly after DHP-PMX in the groups showing improved 2AG and PAI-1 levels (p = 0.0040). The SBP increased significantly in the group showing improved HMGB-1 levels (p < 0.0001). We observed a relationship between hemodynamic improvement and increase of the serum HMGB-1 levels and between improvement of respiratory functions and increase of the serum 2-AG and PAI-1 levels in septic shock patients treated with DHP-PMX.     

Polymyxin B-immobilized fiber hemoperfusion attenuates increased plasma atrial natriuretic peptide and brain natriuretic Peptide levels in patients with septic shock

Polymyxin B-immobilized fiber (PMX-F) hemoperfusion is reported to be safe and effective in septic shock patients. Because atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) may have pathophysiologic significance in the cardiac dysfunction of septic shock patients, we conducted a study to determine whether PMX-F treatment affects plasma ANP and BNP levels in patients with septic shock. Fifty septic shock patients (34 men and 16 women; mean age 60.0 years) and 30 healthy volunteers (18 men and 12 women; mean age 56.0 years) were included in this study. Polymyxin B-immobilized fiber treatment was performed twice, separated by an interval of 24 hours. Blood endotoxin, interleukin (IL)-6, ANP, and BNP levels were measured before, immediately after the second PMX-F treatment, and the following day. In comparing patients with septic shock with healthy control subjects, we found significant increases in plasma endotoxin (p < 0.001), IL-6 (p < 0.001), ANP (p < 0.001), and BNP (p < 0.001). After the second PMX-F treatment, plasma levels of endotoxin (p < 0.01), IL-6 (p < 0.01), ANP (p < 0.01), and BNP (p < 0.01) were reduced significantly. Values decreased further the following day. Both plasma ANP and BNP levels are increased in septic shock patients and PMX-F treatment is effective in reducing these natriuretic peptide levels.     

Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion in septic patients with trauma

We investigated whether microalbuminuria/urinary creatinine ratio (MACR) is increased in septic patients with trauma and whether polymyxin B immobilized fiber (PMX-F) treatment decreases MACR. Twelve trauma patients without sepsis, 18 trauma patients with sepsis, and 10 healthy controls were included in this study. The 18 trauma patients with sepsis were randomly assigned to one of two groups, PMX-F treatment or conventional treatment. Urinary microalbumin and creatinine were measured before and after treatment. Plasma endotoxin levels were determined by endospecy test. Hemoperfusion with PMX-F was carried out twice, for 2 hours, at a flow rate of 100 ml/min. MACR increased in the 30 trauma patients (5.2+/-2.2 mg/mmol) in comparison to that in the healthy controls (1.0+/-0.6 mg/mmol, p < 0.01). In the 18 trauma patients with sepsis, MACR after sepsis (16.6+/-4.8 mg/mmol) was significantly greater than that before sepsis (5.5+/-2.3 mg/mmol, p < 0.01). There was a significant correlation between plasma endotoxin levels and MACR in septic trauma patients (p < 0.001). MACR was reduced from 17.0+/-5.0 mg/mmol to 4.2+/-1.5 mg/mmol (p < 0.01) with PMX-F, and plasma endotoxin levels were also reduced from 34.5+/-18.5 pg/ml to 10.8+/-6.6 pg/ml (p < 0.01). Neither MACR nor plasma endotoxin levels were affected by conventional treatment, however. In summary, trauma patients with sepsis appear to show increased MACR, and PMX-F therapy may be effective for attenuating the increase in MACR.     

Sustained high serum caspase-3 concentrations and mortality in septic patients

Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.     

Two cases of inflammatory muscle disease presenting with raised serum concentrations of troponin T

Troponins T and I are highly sensitive markers of myocardial injury. However, non-cardiac disorders, such as pulmonary embolism, renal failure, subarachnoid haemorrhage, sepsis, eclampsia, chemotherapy, and inflammatory muscle conditions (dermatomyositis and polymyositis), can also result in raised serum troponin concentrations. This article describes two cases that occurred within a month of each other in Craigavon Area Hospital, whereby conditions unrelated to myocardial ischaemia resulted in raised concentrations of cardiac markers. The first patient, in retrospect, underwent unnecessary investigation as an inpatient in the cardiac ward. Experience gained from this case led to more appropriate consultation and management of the second patient.     

Effects of dialyzer membrane on serum albumin levels in patients receiving hemodialysis

Biocompatibility of the dialyzer membrane has been thought to affect the nutritional status in patients receiving chronic hemodialysis. In a series of patients treated in an outpatient dialysis unit, serum albumin was measured before and after changing the dialyzer membrane from one of cellulose to one of polysulfone. There were 48 patients (25 men and 23 women) who had been on dialysis for a mean duration of 78.6 months. The follow-up period was at least 6 months for each type of membrane. Delivered dose of dialysis was higher using the polysulfone membrane but serum albumin was not affected by a change to the more biocompatible membrane. Nutritional considerations are not important in choosing a membrane for dialysis.     

Temporal association of elevations in serum cardiac troponin T and myocardial oxidative stress after prolonged exercise in rats

The objective of this study was to determine if prolonged exercise resulted in the appearance of cardiac troponin T (cTnT) in serum and whether this was associated with elevated levels of myocardial oxidative stress. Forty-five male Sprague–Dawley rats were randomized into four groups and killed before (PRE-EX), immediately (0HR), 2 (2HR) and 24 h (24HR) after a 3-h bout of swimming with 5% body weight attached to their tail. In all animals serum cTnT was assayed using 3rd generation electrochemiluminescence. In homogenized heart tissue myocardial malondialdehyde (MDA), a marker of lipid peroxidation, glutathione (GSH), and a non-enzymatic estimate of total antioxidant capacity (T-AOC) were assessed spectrophotometrically. At PRE-EX cTnT was undetectable in all animals. At 0HR (median, range: 0.055, 0.020–0.100) and 2HR post-exercise (0.036, 0.016–2.110) cTnT was detectable in all animals (P < 0.05). At 24HR post-exercise cTnT was undetectable in all animals. An elevation in MDA was observed 0HR (mean ± SD: 1.7 ± 0.2 nmol mgpro⁻¹) and 2HR (1.6 ± 0.3 nmol mgpro⁻¹) post-exercise compared with PRE-EX (1.3 ± 0.2 nmol mgpro⁻¹; P < 0.05). The antioxidant response to this challenge was a significant (P < 0.05) decrease in GSH 2HR and 24HR post-exercise. Despite this T-AOC did not alter across the trial (P > 0.05). The results indicated that prolonged and strenuous exercise in rats resulted in an elevation in cTnT, a biomarker of cardiomyocyte damage, in all animals 0HR and 2HR after exercise completion. The time course of cTnT elevation was temporally associated with evidence of increased lipid peroxidation in the rat heart.     

Comparison of cardiac troponin I levels in serum and sodium-citrate plasma using the ACCESS 2 immunoassay

The aim of this study was to determine if sodium-citrate plasma is a suitable substitute for serum for cardiac troponin I (cTnI) measurement using the Beckman ACCESS 2 immunoassay. Linear regression analysis of cTnI levels in paired serum and sodium-citrate plasma samples from 80 patients provided a y-intercept of -0.0193 and a slope of 1.044. The correlation was good [r=0.995; 95% confidence interval 1.017 to 1.068, p <0.0001]. The paired results were not significantly different by Student's t-test. Serum and sodium-citrate plasma appear to be interchangeable as samples for cTnI measurement using the ACCESS 2 assay. Furthermore, the use of plasma reduces the turnaround time and may avoid false positive cTnI results due to residual fibrin.     

Elevation of pro-inflammatory cytokines, C-reactive protein and cardiac troponin T in chronic renal failure patients on dialysis

Chronic renal failure (CRF) patients suffer from a chronic inflammation. They are at increased risk of cardiovascular disease. In order to investigate this inflammatory process and cardiovascular risk factors associated with haemodialysis (HD) and peritoneal dialysis (PD), we compared serum/plasma pro-inflammatory cytokines, C-reactive protein (CRP), and cardiac troponin T (cTnT) of 146 CRF patients treated or not treated with PD or HD. Serum cytokines and CRP as well as plasma cTnT were measured by enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and electrochemiluminescence immunoassay, respectively. Results indicated that serum interleukin (IL)-18 concentrations were significantly higher in PD and low creatinine clearance pre-dialysis CRF (LCC) patients than HD patients (both p < 0.05). IL-6 and tumour necrosis factor (TNF)-alpha concentrations were significantly higher in PD patients than LCC patients (both p < 0.01). Serum hsCRP and plasma cTnT in HD were significantly higher than LCC (both p < 0.01). The elevation of pro-inflammatory cytokines should play an important role in the chronic inflammation and increased cardiovascular risk of CRF patients on dialysis. We are evaluating further the diagnostic and prognostic applications of pro-inflammatory cytokines and biochemical inflammatory markers for these patients.     

Evaluation of serum troponin T measurement in acute myocardial infarction]

A monoclonal solid phase enzyme immunoassay has been developed for the detection of human troponin T. The serum troponin T levels in healthy subjects gave 0.05 +/- 0.06 ng/ml in total (n = 176), 0.06 +/- 0.07 ng/ml in males (n = 79) and 0.03 +/- 0.05 ng/ml in females. Within-run and between-run precision (CVs) of the assay were less than 5%. Various common interferents tested did not affect on the assay, but higher titer of rheumatoid factor, and anti-coagulants such as EDTA, heparin oxalate and citrate affected the assay. In all patients with defined acute myocardial infarction, serum troponin T levels increased 7 to 10 folds the upper reference range within 6 hours after the onset of chest pains and maximum elevation of serum troponin T level was at around 20 hours and its levels remained elevated for 7 to 20 days. Specificity and sensitivity for acute myocardial infarction was 92.4% and 100%, respectively. The results indicated that troponin T measurement improved the diagnostic efficiency for the detection of myocardial necrosis as compared with conventionally used cardiac enzymes and was an effective tool for the confirmation of the reperfusion by PTCA and PTCR.     

The prognostic value of serum troponin T in unstable angina.

BACKGROUND. Cardiac troponin T is a regulatory contractile protein not normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage. We used a newly developed enzyme immunoassay for troponin T to determine whether its presence in the serum of patients with unstable angina was a prognostic indicator. METHODS. We screened 109 patients with unstable angina (25 with accelerated or subacute angina and 84 with acute angina at rest) for serum creatine kinase activity, creatine kinase isoenzyme MB activity, and troponin T every eight hours for two days after admission to the hospital. The outcomes of interest during the hospitalization were death and myocardial infarction. RESULTS. Troponin T was detected (range, 0.20 to 3.64 micrograms per liter; mean, 0.78; median, 0.50) in the serum of 33 of the 84 patients (39 percent) with acute angina at rest. Only three of these patients had elevated creatine kinase MB activity (two were positive for troponin T, and one was negative). Of the 33 patients who were positive for troponin T, 10 (30 percent) had myocardial infarction (3 after coronary-artery bypass surgery), and 5 of these died during hospitalization. In contrast, only 1 of the 51 patients with angina at rest who were negative for troponin T had an acute myocardial infarction (P less than 0.001), and this patient died (P = 0.03). Thus, 10 of the 11 patients with myocardial infarctions had detectable levels of troponin T; only 1 had elevated creatine kinase MB activity. Troponin T was not detected in any of the 25 patients with accelerated or subacute angina, and none of these patients died. CONCLUSIONS. Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial-cell injury than serum creatine kinase MB activity, and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina.