CA 15-3 as an alternative marker for KL-6 in fibrotic lung diseases.

BACKGROUND: KL-6 is a mucin that is increased in interstitial lung diseases (ILD), and in some malignancies. CA 15-3, a tumor marker for breast cancer, refers to the same mucin but utilizes antibodies against different epitopes. OBJECTIVE: The aim of our study was to evaluate CA 15-3 as a viable alternative to KL-6 as a for ILDs with and without fibrosis. DESIGN: Serum from 242 patients with ILDs and from 327 healthy controls were included and KL-6 and CA 15-3 were measured in all subjects. Regression analyses and ROC curves were used to compare the performances of both markers. RESULTS: KL-6 and CA 15-3 levels were both significantly higher in the ILD patients compared to the controls (p < 0.0001). A weak yet significant correlation was found between serum KL-6 and CA 15-3 levels in the controls (R = 0.39, p < 0.0001), but showed a much higher correlation in the patient group (R = 0.85, p < 0.0001). CA 15-3 correlated best with KL-6 in patients with fibrotic ILDs (R = 0.83, p < 0.0001). KL-6 performed better as a marker compared to CA 15-3 in most ILDs. Both markers performed best in identifying idiopathic pulmonary fibrosis (IPF) and were equally able to differentiate between ILDs with and without fibrosis: (sensitivity and specificity %): 100/97, 95/92, and 90/72, respectively. CONCLUSION: CA 15-3 and KL-6 are equally sensitive and specific in terms of differentiating between ILDs with and without fibrosis. The wide availability, ease of use, and cost effectiveness, make CA 15-3 a viable alternative for KL-6 as a possible marker for pulmonary fibrosis.

Measurements of cerebrospinal fluid concentrations of S100beta protein during and after thoracic endovascular stent grafting.

OBJECTIVES: Thoracic endovascular aortic repair is associated with postoperative spinal cord ischemia in approximately 1 to 12.5% of all cases. S100beta is a protein that is released during acute damage of the central nervous system. This study was performed to determine the concentration of S100beta in cerebrospinal fluid during and after stenting of the thoracic aorta in patients at high risk for spinal cord ischemia. DESIGN: Prospective clinical study. MATERIALS AND METHODS: Eight patients who underwent elective thoracic aortic stent grafting underwent lumbar spinal fluid drainage. These patients were at high risk to develop spinal cord ischemia. METHODS: CSF samples for analysis of S100beta protein were drawn after induction of anesthesia, during stenting, once every hour the following six hours and 20 hours after repair. RESULTS: No significant increase in S100beta protein could be detected in CSF and no neurological deficits were detected postoperatively. CONCLUSIONS: The results of this study show us that there is no significant release of S100beta protein in CSF during stenting of the thoracic aorta in this subgroup of patients at high risk for spinal cord ischemia, consistent with clinical exam that there was no significant damage to the central nervous system.

Inhibition of platelet function by abciximab or high-dose tirofiban in patients with STEMI undergoing primary PCI: a randomised trial.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, few data exist on the magnitude of platelet activation, aggregation and dosing of glycoprotein (GP) IIb/IIIa receptor inhibitors. METHODS: Sixty STEMI patients were randomised to abciximab, to high-dose tirofiban or to no additional GP IIb/IIIa inhibitor treatment. Platelet activation (P-selectin expression) was measured using flow cytometry and the level of inhibition of platelet aggregation was assessed using the Plateletworks assay. Additionally, the PFA-100 with the collagen/adenosine-diphosphate cartridge (CADP) was used to compare the levels of platelet inhibition. All measurements were performed at baseline (T(0)), immediately after (T(1)), 30 minutes (T(2)), 60 minutes (T(3)) and 120 minutes (T(4)) after primary PCI. RESULTS: The level of platelet activation in both GP IIb/IIIa receptor inhibitor treated groups was significantly lower compared with the control group at all time points after primary PCI (p=0.04). Also the administration of the currently recommended dose of abciximab resulted in significantly lower levels of inhibition of aggregation compared with high-dose tirofiban (p<0.0001). In addition, the CADP closure times were significantly prolonged in both GP IIb/IIIa inhibitor treated groups compared with the control group at time points T(1) (p=0.006) and T(4) (p<0.0001). CONCLUSION: The administration of high-dose tirofiban resulted in a significantly higher inhibition of platelet aggregation compared with the currently recommended dose of abciximab. Large clinical trials are needed to assess whether this laboratory superiority of high-dose tirofiban translates into higher clinical efficacy. (Neth Heart J 2007;15:375-81.).

Significant reduction in blood loss in patients undergoing minimal extracorporeal circulation.

Several recent studies have shown differences in blood loss and allogeneic transfusion requirements between on-pump and off-pump coronary artery bypass grafting (CABG). Recently a new concept, the mini-extracorporeal circulation, was introduced to minimize the side effects of extracorporeal circulation. Therefore, there are no data comparing the three techniques with special emphasis to blood loss and transfusion requirements. Two hundred and eighty-five patients undergoing first-time coronary artery bypass grafting were retrospectively matched for number of grafts, age and sex. Ninety-five patients underwent surgery with the off-pump CABG (OPCAB) technique, 97 patients using conventional CABG with cold cardioplegia (CCABG) and 93 patients with the mini-extracorporeal circuit with warm blood cardioplegia (MCABG). Blood loss for the CCABG group with a mean loss of 819 +/- 557 mL and the OPCAB group with a mean loss of 870 +/- 768 mL was significant different compared to the MCABG group with a mean loss of 679 +/- 290 mL. The use of units red blood cell units was significantly higher for CCABG group and OPCAB group compared to the MCABG group. On the day of operation the use of platelet concentrate was significantly higher for the CCABG group compared to MCABG group. As a consequence of improvements of several components of the mini heart lung machine, significantly less blood products are needed in MCABG patients. The expected reduced need for transfusion when the pump was completely avoided could not be confirmed in this single retrospective cohort study.

Pneumoproteins as a lung-specific biomarker of alveolar permeability in conventional on-pump coronary artery bypass graft surgery vs mini-extracorporeal circuit: a pilot study.

BACKGROUND: Despite improvements of the heart-lung machine (HLM), oxidative stress and subsequent damage to the alveolar capillary membrane still occur after conventional on-pump coronary artery bypass graft (CCABG) surgery. In an attempt to further improve the conventional HLM, a mini-extracorporeal circuit (MECC) was introduced. This new concept is based on minimal volume shifts. The extent of alveolar injury that is associated with this new technique is unknown. The lung-specific biomarkers Clara-cell 16 (CC16) and KL-6 are applied in this study to quantify alveolar dysfunction in both techniques. METHODS: In a prospective observational setting, the concentrations of CC16 and KL-6 were measured during and after 10 consecutive CCABG operations and 10 consecutive coronary artery bypass graft (CABG) operations using MECC (MCABGs). These pneumoproteins were measured after the induction of anesthesia, before clamping of the ascending aorta, after unclamping of the aorta, on arrival to the ICU, and on the following days until discharge. Quantification of the differences of KL-6 and CC16 leakage through the alveolar membranes between the two techniques was realized by calculation of the Student t test. Perioperative and postoperative shunt fractions and clinical observations were monitored simultaneously. The potential value of pneumoproteins as biomarkers for quantification of alveolar permeability during CABG surgery was tested. RESULTS: Significantly reduced concentrations of CC16 were found early after MCABG as compared to CCABG surgery (p = 0.033). KL-6 showed no consistent pattern during both treatment modalities. Early after CCABG surgery, shunt fractions tended to show reduced oxygen transport over the alveolar membrane as compared to MCABG surgery. CONCLUSION: CC16 appears to be a useful biomarker for alveolar permeability during CABG surgery. Injury of the alveolar capillary membrane appears significantly reduced during MCABG surgery. Consistently early postoperative alveolar shunt fractions showed an increased value in CCABG compared to MCABG surgery in the early postoperative phase. Further randomized studies need to confirm the value of CC16 as marker in monitoring alveolar capillary damage during coronary bypass grafting.

Mini extracorporeal circuit for coronary artery bypass grafting: initial clinical and biochemical results: a comparison with conventional and off-pump coronary artery bypass grafts concerning global oxidative stress and alveolar function.

BACKGROUND: The new concept of mini-extracorporeal circulation (MECC) for coronary artery bypass grafts (MCABG) consists of minimal priming volume, a heparin-coated closed circuit, a centrifugal pump, active drainage, blood cardioplegia and a cell-saving device. The potential organ protective effect of this technique during CABG is unknown. Initial clinical outcomes, oxidative stress, alveolar shunting and need for blood transfusion were investigated for MCABG patients. Sub-sets of these data were compared to outcomes of matched groups of patients operated conventionally (CCABG) and off-pump (OPCAB). METHODS: Data of 184 patients were gathered and analysed from a prospective observational database system. This database consists of the initial experience with the first 114 MCABG operations. Of these, the clinical outcome was investigated. In a subset of 60 MCABGs, need for transfusion was monitored and compared to 60 CCABGs. Serum concentrations of malondialdehyde (MDA), allantoin/urate ratios, shunt fractions and lung epithelium-specific proteins (CC16) were measured as biomarkers of damage during MCABG, CCABG and OPCAB (n =30). RESULTS: Patient groups were similar concerning age, risk and number of distal anastomoses. Clinical outcomes are shown for MCABGs only. During MCABG, need for transfusion was significantly reduced compared to CCABG (p < 0.001). Serum concentrations of MDA and allantoin/urate ratios showed significantly reduced oxidative stress during MCABG compared to CCABG. During MCABG, F-shunts were reduced shortly after surgery. Increased concentrations of pneumoprotein CC16 were measured during CCABG compared to MCABG (data submitted). CONCLUSION: Short-term clinical outcomes of MCABG patients are satisfactory. Compared to CCABG the need for transfusion is significantly reduced when a MECC is used. Oxidative stress parameters show a tendency towards improved global organ protection compared to CCABG. F-shunt fractions and CC16 concentrations suggest reduced alveolar damage during MCABG. In a prospective study, the protective effect of mini-CABG has to be confirmed.

The usefulness of five D-dimer assays in the exclusion of deep venous thrombosis.

D-Dimer measurement is a promising tool in the exclusion of venous thrombosis. New d-dimer assays have been introduced, but need clinical validation. Our objective was to evaluate the clinical usefulness of four relatively new d-dimer assays and a classical ELISA in outpatients suspected for deep venous thrombosis. In 537 patients, participants in a large prospective management study using a clinical probability score and a d-dimer measurement (Tina-quant), additional samples were taken for d-dimer measurement using the Asserachrom ELISA, the VIDAS New, the STA-LIA and the Miniquant assay. Performances of each test were calculated using clinical data during a 3-month follow-up. Thrombosis was detected in 224 patients (42%). The area under the ROC curve was significantly higher for the Tina-quant as compared to the other assays. Using standard cut-off values, sensitivity, negative predictive value (NPV) and specificity of the Asserachrom were 97, 94 and 33%, respectively. For the VIDAS New, values were 100, 96 and 8%, respectively. The Tina-quant showed values of 99, 98 and 41%, respectively, and the STA-LIA 98, 95 and 32%. Values for the Miniquant were 95, 94 and 52%. The d-dimer assays in our study all show a high sensitivity and negative predictive value, but none of the assays reached an NPV of > 98% at standard cut-off values. d-Dimer assays with a low specificity still necessitate additional diagnostic tests in the majority of the patients.

S100 protein content of umbilical cord blood in healthy newborns in relation to mode of delivery.

BACKGROUND: Early detection and quantification of brain damage in neonatal asphyxia is important. In adults, S100 protein in blood is associated with damage to the central nervous system. OBJECTIVE: To determine whether S100 protein can be detected in arterial and venous cord blood of healthy newborns and to relate S100 protein concentrations in cord blood to mode of delivery. METHOD: S100 protein levels in umbilical cord blood of 81 healthy infants were determined. RESULTS: S100 protein was present in arterial (median concentration 1.62 micro g/l) and venous (median concentration 1.36 micro g/l) cord blood. Levels were significantly higher in vaginal births (median arterial concentration 1.72 micro g/l; median venous concentration 1.48 micro g/l) than births by caesarean section (1.51 micro g/l and 1.26 micro g/l respectively). CONCLUSION: More research is necessary to determine whether S100 protein is a useful marker in neonatal asphyxia.

Off-pump versus on-pump coronary artery bypass grafting: oxidative stress and renal function.

OBJECTIVES: Oxidative stress and renal dysfunction occur in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (on-pump CABG). Whether the same adverse effects also occur during off-pump CABG is the question in this study. METHODS: Forty patients, 27 men and 13 women, undergoing elective CABG were included; 20 patients underwent on-pump CABG and 20 patients underwent off-pump CABG. Renal and ischemia/reperfusion injury parameters were studied, as well as malondialdehyde as a parameter for oxidative stress. RESULTS: The renal function measured as the mean urinary creatinine excretion decreased significantly during surgery for the on-pump CABG group from 7.62+/-4.74 before surgery to 3.07+/-1.49 mmol/l after surgery, whereas no changes occurred in the off-pump CABG group. The mean urinary concentrations of hypoxanthine, xanthine and malondialdehyde expressed as creatinine ratios for the on-pump group increased significantly from 1.92+/-1.36, 6.06+/-3.62 and 0.21+/-0.07 before surgery to 11.88+/-5.77, 13.11+/-6.61 and 0.57+/-0.31 mmol/mol creatinine, respectively at arrival to the intensive care unit (ICU). During the next time-points, the purines and malondialdehyde decreased to 9.21+/-7.46, 7.55+/-3.95 and 0.32+/-0.13 mmol/mol creatinine, respectively after a 20 h stay at the ICU. For the off-pump CABG group, the mean ratios also increased significantly from 1.71+/-1.38, 2.01+/-0.96 and 0.16+/-0.10 before surgery to 4.73+/-3.19, 5.15+/-3.74 and 0.23+/-0.17 mmol/mol creatinine, respectively at arrival to the ICU. During the next time-points, the ratios of xanthine and malondialdehyde decreased to 3.80+/-2.92 and 0.24+/-0.13 mmol/mol creatinine, respectively. The ratio for hypoxanthine reached the highest ratio (6.97+/-5.67 mmol/mol creatinine) after a 9 h stay at the ICU, after which the ratio decreased to 5.98+/-5.56 mmol/mol creatinine after a 20 h stay at the ICU. However, all ratios from the on- and off-pump CABG patients still remained elevated compared with preoperative ratios. In addition, all ratios for the on-pump CABG group were elevated significantly at all time-points for xanthine, at time-points T2 and T4 for hypoxanthine and at time-point T2 for malondialdehyde as compared with the off-pump CABG group. CONCLUSIONS: Only mild signs of oxidative stress and no renal dysfunction were found during and after off-pump CABG compared with on-pump CABG.

Oxidative stress after lung resection therapy: A pilot study.

STUDY OBJECTIVES: To investigate whether oxidative stress occurs following lobectomy and pneumonectomy and to evaluate whether markers of oxidative stress might be of value in the assessment of the diagnosis, course, and prognosis of postoperative complications. DESIGN: A prospective study. SETTING: A specialized thoracic surgical unit in a large referral hospital. PATIENTS: Twenty-eight patients with lung carcinoma undergoing thoracotomy. MEASUREMENTS: Exhaled H(2)O(2) concentrations in breath condensate were measured by spectrophotometry, while malondialdehyde (MDA) levels in urine samples collected every 24 h were measured by reversed-phase, ion-pair high-performance liquid chromatography using ultraviolet detection. RESULTS: Our results show increased H(2)O(2) and MDA levels in lobectomy patients compared with pneumonectomy patients. A strong correlation was found between the levels of H(2)O(2) and MDA. CONCLUSION: The present data support the hypothesis that oxidative stress may occur following pulmonary resection.

Influence of folic acid on postprandial endothelial dysfunction.

Triglyceride-rich lipoproteins that circulate postprandially are increasingly being recognized as potentially atherogenic. These particles also have been shown to cause endothelial dysfunction. We recently demonstrated that acute parenteral administration of folic acid restores endothelial function in vivo in patients with increased LDL cholesterol levels. In vitro data suggested that this effect could be mediated by a reduction of radical stress. In the present study, therefore, we evaluated the effect of an acute oral fat load on both endothelial function and oxygen radical production. Next, we studied whether 2 weeks of pretreatment with 10 mg folic acid PO could prevent these fat-induced changes. We conducted a prospective, randomized, placebo-controlled study to evaluate the effect of oral folic acid administration (10 mg/d for 2 weeks) on basal endothelial function as well as endothelial function on an acute fat load in 20 healthy volunteers 18 to 33 years old. Endothelial function was assessed as flow-mediated dilatation (FMD). Endothelium-independent dilatation was measured after sublingual nitroglycerin spray. Oxygen radical stress was assessed by measurement of the urinary excretion of the stable radical-damage end product malondialdehyde. During administration of placebo, FMD decreased significantly after an acute oral fat load, with a median from 10.6% (8.3% to 12.2%) to 5.8% (3.0% to 10.2%), P<0.05. During folic acid administration, FMD was unaffected by a fat load, with a median from 9.6% (7.1% to 12.8%) to 9.9% (7.5% to 14.1%), P=NS. The increase in malondialdehyde excretion in the urine after fat loading was also prevented during folic acid administration (absolute increase after an acute fat load during placebo, 0.11+/-0.1 micromol/L versus folic acid, 0.02+/-0.1 micromol/L, P<0.05). The response to the endothelium-independent vasodilator nitroglycerin remained unaltered throughout the study. Pretreatment with oral folic acid prevents the lipid-induced decrease in FMD as well as the lipid-induced increase in urinary radical-damage end products. Because these observations were made in healthy volunteers with normal folate and homocysteine levels, it is suggested that a higher folate intake in the general population may have vasculoprotective effects.

Indices of oxidative stress in urine of patients undergoing coronary artery bypass grafting.

Indices of oxidative stress in urine were measured in twenty patients undergoing elective coronary artery bypass grafting. Hypoxanthine, xanthine and uric acid were measured in urine, as markers of ischaemia together with malondialdehyde, which is a marker for lipid peroxidation. To correct for renal dysfunction during coronary artery bypass grafting the creatinine concentration was measured in urine and plasma. The creatinine concentration in plasma increases significantly during surgery, from 84 +/- 23 mumol/l to 133 +/- 52 mumol/l, whereas the creatinine concentration in urine decreases significantly, from 8.29 +/- 4.45 mmol/l to 2.70 +/- 1.01 mmol/l, during reperfusion. For reasons of comparison, the values of the observed measurements in urine are expressed per mol creatinine. The hypoxanthine and xanthine excretions both increase significantly, from 15.0 +/- 7.3 and 10.9 +/- 5.7 mmol/mol creatinine, respectively, after induction of anaesthesia to a maximum of 33.1 +/- 16.7 and 17.4 +/- 11.1 mmol/mol creatinine, respectively, during reperfusion. The malondialdehyde excretion increases significantly, from 1.38 +/- 0.80 mmol/mol creatinine after induction of anaesthesia to a maximum of 3.87 +/- 1.87 mmol/mol creatinine during reperfusion. The purines and malondialdehyde in urine (expressed as a ratio of creatinine), increase during coronary artery bypass grafting as a consequence of oxygen mediated tissue injury.