Computational Decision Support for PE Diagnosis based on Ventilation Perfusion Ratio.

AIM: The aim of this study is to investigate whether computer-aided, semi-automated 3D lung lobe quantification can support decision-making on PE diagnosis based on the ventilation-perfusion ratio in clinical practice. METHODS: A study cohort of 100 patients (39 male, 61 female, age 64.8±15.8 years) underwent ventilation/perfusion single photon emission computed tomography (V/Q-SPECT/CT) to exclude acute PE on SPECT/CT OPTIMA NM/CT 640 (GE Healthcare). Two 3D lung lobe quantification software tools (Q. Lung: Xeleris 4.0, GE Healthcare and LLQ: Hermes Hybrid 3D Lung Lobar Quantification, Hermes Medical Solutions) were used to evaluate the numerical lobar ventilation/perfusion ratio (VQR) and lobar volume/perfusion ratio (VPR). A test of linearity and equivalence of the two 3D software tools was performed using Pearson, Spearman, quadratic weighted kappa and the mean squared deviation for VPR/VQR. An algorithm was developed that identified PE candidates using ROC analysis. The agreement between the PE findings of an experienced nuclear medicine expert and the calculated PE candidates was represented by the magnitude of the YOUDEN index (J) and the size of the area under the receiver operating curve (AUC). RESULTS: Both 3D software tools showed good comparability. The YOUDEN index for QLUNG(VPR/VQR)/LLQ(VPR/VQR) was in the range from 0.2 to 0.5. The mean AUC averaged over all lung lobes for QLUNG(VPR) was 0.66, CI95%: ±14.0%, for QLUNG(VQR) 0.66, CI95%: ±13.3%, for LLQ(VPR) 0.64, CI95%: ±14.7% and for LLQ(VQR) 0.65, CI95%: ±13.1%. CONCLUSION: This study reveals that 3D software tools are feasible for numerical PE detection. The clinical decision can be supported by using a numerical algorithm based on ROC analysis.

Anatomical acromioclavicular joint stabilization with chemically sterilized tendon allografts: A retrospective study.

Background: The purpose of this retrospective study was to analyze whether chemically sterilized tendon allografts perform as well as other non-sterilized allografts and autografts as described in the literature for anatomical acromioclavicular joint stabilization for the treatment of Rockwood III-V. Allografts are still described as a factor for higher re-rupture rates. Methods: Retrospective data were collected from 21 acromioclavicular joint stabilizations performed by a single surgeon and performed between 2011 and 2014 using sterilized semitendinosus allografts. The primary endpoints were re-rupture and complication rates. Secondary endpoints were AC-joint stability, pain level, return to work and sport and the range of motion. Results: No re-ruptures occurred during the mean follow-up time of 33 months. Zero complications occurred directly after surgery, but three complications later than three weeks after surgery. All cases resolved without further surgery. After surgery, stability significantly improved for all patients. Post-surgery, 19 patients had stable acromioclavicular joints and only two patients showed minor instabilities. Range of motion returned to the range of the healthy shoulders for all patients. Conclusion: Chemically sterilized semitendinosus allograft use for anatomic AC-joint stabilization is equivalent to the use of other allografts or autografts and required no hardware removal. No donor age or graft size dependence was observed, due to zero re-ruptures.

[Chronic pancreatitis]. / Chronische Pankreatitis.

Chronic pancreatitis is characterized by recurrent abdominal pain due to chronic inflammation resulting in loss of exocrine and endocrine function. The main complications of chronic pancreatitis are pancreatic pseudocysts and pancreatic carcinoma. In most cases chronic pancreatitis is induced by excessive chronic alcoholism, but intake of small amounts of alcohol may be enough to induce chronic pancreatitis. Treatment of pain includes discontinuation of alcohol abuse, use of analgetics and endoscopic interventional and surgical treatment options.

Clopidogrel response status assessed with Multiplate point-of-care analysis and the incidence and timing of stent thrombosis over six months following coronary stenting.

Clopidogrel low-responsiveness assessed with multiple electrode platelet aggregometry (MEA) has been shown to be a strong and independent predictor of early stent thrombosis (ST) after coronary stenting. The relation of clopidogrel response status, as assessed with MEA, with incidence and timing of ST during an extended follow-up period has never been reported. Here, we report the six-month follow-up results of a prospective trial assessing clopidogrel responsiveness with MEA in patients undergoing percutaneous coronary intervention (PCI). A total of 1,608 consecutive patients with planned drug-eluting stent placement were enrolled in this study. Before PCI patients uniformly received 600 mg clopidogrel and blood was taken directly before PCI to measure ADP-induced platelet aggregation with MEA. The upper quintile (20%) of patients according to MEA measurements (n=323) was defined as clopidogrel low responders. Compared with normal responders (n=1,285), the cumulative incidence of definite ST within six months was significantly higher in low responders [2.5% vs. 0.4%; OR 6.5; 95% CI, 2.4-17.0; P<0.001]. The combined incidence of definite or probable ST was higher as well in low vs. normal responders [4.1% vs. 0.7%; OR 5.8; 95% CI, 2.8-12.3; P<0.0001]. A significant inverse correlation of MEA values and the timing of definite or probable ST (in days) was observed (Spearman coefficient = -0.45; P=0.04) with events occurring earlier in the low-responder group. MEA measurements are highly predictive for the occurrence of ST during the first six months following coronary stenting. In the majority of clopidogrel low responders suffering ST, the ischaemic event occurs early in the course after the procedure.

Assessment of platelet response to clopidogrel with multiple electrode aggregometry, the VerifyNow P2Y12 analyzer and platelet Vasodilator-Stimulated Phosphoprotein flow cytometry.

Multiple electrode platelet aggregometry (MEA) adenosine diphosphate (ADP) test is able to detect the platelet response to clopidogrel. The values obtained with MEA ADPtest correlate with those obtained with light transmission aggregometry and peri-interventional MEA ADPtest measurements are highly associated with the risk of early stent thrombosis after percutaneous coronary intervention. The main purpose of the present study was to correlate MEA ADPtest with the VerifyNow P2Y12 analyzer, Platelet VASP flow cytometry and the MEA ADPtest HS in order to test if these assays can substitute for each other. Blood samples from 60 consecutive patients scheduled for coronary angiography before and after administration of 600 mg of clopidogrel were analyzed. The correlation of MEA ADPtest with the other whole blood tests was moderate. The following order for the degree of correlation with MEA ADPtest for postclopidogrel values was found: MEA ADPtest HS (R = 0.83) > VerifyNow P2Y12 (R = 0.47) > Platelet VASP (R = 0.35). Of the 12 patients in the upper quintile of postclopidogrel values according to MEA ADPtest, seven were in the upper quintile according to VerifyNow P2Y12 (P < 0.001), six were in the upper quintile according to MEA ADPtest HS (P = 0.004) and three were in the upper quintile according to VASP (P = 0.63). Therefore, the studied whole blood assays cannot substitute for each other. Each assay with prognostic significance will have to undergo the ultimate test for individualized antiplatelet therapy in form of an adequately powered randomized clinical trial that shows that adjustment of antiplatelet therapy is beneficial for the patient.

Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel.

Patients receiving dual antiplatelet treatment with aspirin and clopidogrel are commonly treated with proton pump inhibitors (PPIs). Attenuating effects on platelet response to clopidogrel have been reported solely for the PPI omeprazole. PPIs differ in their metabolisation properties as well as their potential for drug-drug interactions. The aim of this study was to investigate the impact of different PPIs (pantoprazole, omeprazole, esomeprazole) on platelet response to clopidogrel in patients with previous coronary stent placement under chronic clopidogrel treatment. In a cross-sectional observational study, consecutive patients under clopidogrel maintenance treatment (n = 1,000) scheduled for a control coronary angiography were enrolled. Adenosine diphosphate (ADP)-induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry (MEA). From the entire study population, 268 (26.8%) patients were under PPI treatment at the time point of platelet function testing (pantoprazole, n = 162; omeprazole, n = 64; esomeprazole, n = 42). Platelet aggregation (median [interquartile range]) was significantly higher in patients with omeprazole treatment (295.5 [193.5-571.2] AU*min) compared to patients without PPI treatment (220.0 [143.8-388.8] AU*min; p = 0.001). Platelet aggregation was similar in patients with pantoprazole (226.0 [150.0-401.5] AU*min) or esomeprazole (209.0 [134.8-384.8] AU*min) treatment compared to patients without PPI treatment (p = 0.69 and p = 0.88, respectively). Attenuating effects of concomitant PPI treatment on platelet response to clopidogrel were restricted to the use of omeprazole. No attenuating effects on platelet response to clopidogrel were observed for pantoprazole or esomeprazole. Specifically designed and randomized clinical studies are needed to define the impact of concomitant PPI treatment on adverse events after percutaneous coronary intervention.

Platelet reactivity after clopidogrel treatment assessed with point-of-care analysis and early drug-eluting stent thrombosis.

OBJECTIVES: The aim of this prospective trial was to assess whether platelet reactivity to clopidogrel assessed with multiple electrode platelet aggregometry (MEA) correlates with the risk of early drug-eluting stent thrombosis (ST). BACKGROUND: Studies using light transmission aggregometry (LTA) have shown that insufficient suppression of platelet reactivity to adenosine diphosphate (ADP) after clopidogrel treatment is associated with an increased risk of adverse cardiovascular events after percutaneous coronary intervention (PCI). However, LTA is time- and labor-intensive and inconvenient for the routine. A point-of-care assay with similar predictive power would be of great value. METHODS: Between February 2007 and April 2008, a total of 1,608 consecutive patients with coronary artery disease and planned drug-eluting stent implantation were enrolled. Before PCI, all patients received 600 mg clopidogrel. Blood was obtained directly before PCI. The ADP-induced platelet aggregation was assessed in whole blood with MEA on a Multiplate analyzer (Dynabyte, Munich, Germany). The primary end point was definite ST at 30 days. RESULTS: The upper quintile of patients according to MEA measurements (n = 323) was defined as clopidogrel low responders. Compared with normal responders (n = 1,285), low responders had a significantly higher risk of definite ST within 30 days (2.2% vs. 0.2%; odds ratio [OR]: 9.4; 95% confidence interval [CI]: 3.1 to 28.4; p < 0.0001). Mortality rates were 1.2% in low versus 0.4% in normal responders (OR: 3.2; 95% CI: 0.9 to 11.1; p = 0.07). The composite of death or ST was higher in low versus normal responders (3.1% vs. 0.6%; OR: 5.1; 95% CI: 2.2 to 11.6; p < 0.001). CONCLUSIONS: Low response to clopidogrel assessed with MEA is significantly associated with an increased risk of ST. Further studies are warranted to evaluate the ability of MEA to guide antiplatelet therapy in patients undergoing PCI.

Assessment of ADP-induced platelet aggregation with light transmission aggregometry and multiple electrode platelet aggregometry before and after clopidogrel treatment.

The level of platelet aggregation, measured with light transmission aggregometry (LTA) in platelet rich plasma (PRP), has been shown to predict outcomes after percutaneous coronary intervention (PCI). However, measuring parameters of platelet function with LTA is time consuming and weakly standardized. Thus, a fast and standardized method to assess platelet function after clopidogrel treatment would be of great value for clinical practice. A new method, multiple electrode platelet aggregometry (MEA), to rapidly measure platelet aggregation in whole blood has recently been developed. The aim of this study was to assess parameters of platelet function with MEA and LTA before and after administration of 600 mg clopidogrel. Blood samples from 149 patients scheduled for coronary angiography were taken after clopidogrel treatment; in addition, in 60 of the patients samples were available before clopidogrel treatment. ADP-induced platelet aggregation was measured with LTA and simultaneously in whole blood with MEA on the Multiplate analyzer. Platelet aggregation measured with MEA decreased significantly after clopidogrel treatment (P < 0.0001). ADP-induced platelet aggregation assessed with MEA and LTA correlated significantly (Spearman rank correlation coefficient = 0.71; P < 0.0001). The results of MEA, a fast and standardized method to assess the platelet response to ADP prior to and after clopidogrel treatment, correlate well with LTA.

N-terminal pro-brain natriuretic peptide on admission in patients with acute myocardial infarction and correlation with scintigraphic infarct size, efficacy of reperfusion, and prognosis.

We investigated whether N-terminal pro-brain natriuretic peptide (NT-pro-BNP) that was measured on admission in patients with acute myocardial infarction (AMI) predicts the efficacy of reperfusion or whether NT-pro-BNP provides prognostic information independent of infarct size as estimated by single-photon emission computed tomographic scintigraphy. The study included 174 patients with ST-segment elevation AMI who were admitted within 24 hours of pain onset. NT-pro-BNP level was measured on admission. Paired scintigraphic studies (before and 7 to 14 days after reperfusion) were performed to assess infarct size and define myocardial salvage. One-year clinical follow-up was assessed. Patients were categorized into the high NT-pro-BNP group (57 patients in the upper tertile of NT-pro-BNP) and low NT-pro-BNP group (117 patients in the middle and lower tertiles of NT-pro-BNP). Initial median perfusion defect was 35.0% (interquartile rage 20.0 to 53.0%) of the left ventricle in the high NT-pro-BNP group versus 19.0% (interquartile range 10.0 to 32.2) of the left ventricle in the low NT-pro-BNP group (p <0.001). Median salvage index was 0.36 (interquartile range 0.16 to 0.86) in the high NT-pro-BNP group versus 0.53 (interquartile range 0.31 to 0.75) in the low NT-pro-BNP group (p = 0.22). After adjustment in Cox's proportional hazards model, NT-pro-BNP remained an independent correlate of 1-year mortality (adjusted hazard ratio 2.31, 95% confidence interval 1.09 to 4.89, p = 0.03, high vs low NT-pro-BNP group). In conclusion, NT-pro-BNP measured on admission in patients with AMI correlates with scintigraphic area at risk and predicts prognosis but does not predict the efficacy of mechanical reperfusion by stenting or angioplasty.

N-terminal probrain natriuretic peptide and C-reactive protein in stable coronary heart disease.

PURPOSE: C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) provide prognostic information in patients with stable coronary heart disease. The aim of the study was to investigate whether combined use of NT-proBNP and CRP improves risk stratification in these patients. METHODS: This cohort study included 989 patients with stable coronary heart disease who underwent coronary stenting. CRP and NT-proBNP were measured before angiography. The primary end point of the study was all-cause mortality. Using median values of NT-proBNP (279.9 ng/L) and CRP (1.2 mg/L), patients were divided into 4 groups: low NT-proBNP-low CRP group (305 patients with NT-proBNP or =median; high NT-proBNP-low CRP group (237 patients with NT-proBNP> or =median and CRP or =median and CRP> or =median). RESULTS: During a median follow-up of 3.6 years (interquartile range 3.3 to 4.5 years), there were 85 deaths: 6 deaths in the low NT-proBNP-low CRP group, 11 deaths in the low NT-proBNP-high CRP group, 20 deaths in the high NT-proBNP-low CRP group, and 48 deaths in the high NT-proBNP-high CRP group with Kaplan-Meier mortality estimates of 2.7%, 8.9%, 12.1% and 35.6%, respectively (P <.001). Cox proportional hazards model showed that combination NT-proBNP-CRP was the strongest independent correlate of mortality (hazard ratio [HR] 4.3, 95% confidence interval [CI], 2.0-9.3; P <.001 for high NT-proBNP-high CRP vs low NT-proBNP-low CRP). CONCLUSION: Combined use of NT-proBNP and CRP improves long-term risk prediction of mortality in patients with stable coronary heart disease.

Iron status and clinical outcome in patients with coronary artery disease after coronary stenting.

BACKGROUND AND AIM: So far, no studies have assessed whether there is an association between iron status and the incidence of major adverse cardiac events or restenosis after coronary stenting. We conducted this study to investigate whether there is an association between body iron status and clinical outcome in patients with coronary artery disease after coronary stenting. METHODS AND RESULTS: The study included 664 patients with coronary artery disease who underwent coronary stent implantation. The soluble transferring receptor/ferritin ratio (sTfR/ferritin ratio) was used as an index of iron status. Patients were divided into three groups according to the tertiles of sTfR/ferritin ratio: lower tertile (<11.9; n = 221), middle tertile (11.9-27.8; n = 221) and upper tertile (>27.8; n = 222). The combined incidence of major adverse cardiac events (death, myocardial infarction and target vessel revascularization) was the primary end point of the study. Patients in the lower tertile of the sTfR/ferritin ratio presented more often with unstable angina or acute myocardial infarction and had longer lesions and higher grade of stenosis than the patients in the middle or upper tertile of the sTfR/ferritin ratio. Angiographic restenosis at 6-month angiography was also evaluated. The cumulative event rate of composite end point of death, myocardial infarction or target vessel revascularization was 27.6% in patients in the lower tertile, 24.4% in patients in the middle tertile and 28.4% in patients in the upper tertile of the sTfR/ferritin ratio (p = 0.68). Restenosis was found in 27.8% (n = 45) in the lower tertile, 25.8% (n = 42) in the middle tertile and 27.5% (n = 38) in the upper tertile of the sTfR/ferritin ratio (p = 0.90). CONCLUSIONS: Our study showed no association between iron status and the incidence of major adverse cardiac events or angiographic coronary restenosis in patients with coronary artery disease after coronary stenting.

Prognostic value of N-terminal pro-brain natriuretic peptide in patients with chronic stable angina.

BACKGROUND: Patients with chronic stable angina are poorly characterized in terms of biomarkers that help in the assessment of prognosis. We investigated whether plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) may be used as a prognostic marker in patients with chronic stable angina treated with coronary stenting. METHODS AND RESULTS: Plasma levels of NT-proBNP were measured in 1059 patients with chronic stable angina and coronary angiographic confirmation of significant coronary artery disease. The primary end point of the study was mortality. After a median of 3.6 years (interquartile range, 3.3 to 4.5 years), there were 106 deaths. Kaplan-Meier estimates of 5-year mortality were 4.7% in the first quartile, 7.8% in the second quartile, 11.4% in the third quartile, and 32.7% in the fourth quartile of NT-proBNP (P<0.001). A Cox proportional hazards model showed that NT-proBNP was the strongest correlate of mortality (adjusted hazards ratio [HR], 5.83 [95% confidence interval: 2.07 to 16.44] for the fourth versus the first quartile). A similar prognostic value of NT-proBNP was demonstrated for cardiovascular mortality (HR, 5.98 [1.55 to 23.13] for the fourth versus the first quartile) and for patients with New York Heart Association class I and II (HR, 6.03 [2.07 to 17.52] for the fourth versus the first quartile). CONCLUSIONS: Circulating levels of NT-proBNP are a strong prognostic biomarker for patients with chronic stable angina.

Lack of association between circulating levels of plasma oxidized low-density lipoproteins and clinical outcome after coronary stenting.

BACKGROUND: We undertook this study to investigate whether there is an association between circulating oxidized low-density lipoproteins (OxLDLs) and outcome after coronary stenting. METHODS: The study included 687 patients with coronary artery disease who underwent coronary stenting. Oxidized low-density lipoproteins were measured before coronary angiography. The median of OxLDL concentrations was 67.7 U/L. Patients were divided into 2 groups: the group with OxLDL levels < median (low OxLDL group, n = 345) and the group with OxLDL levels > or = median (high OxLDL group, n = 342). The combined incidence of major adverse cardiac events (death, myocardial infarction, and target vessel revascularization) was the primary end point. Angiographic restenosis was also evaluated. RESULTS: The combined incidence of death, myocardial infarction, and target vessel revascularization was 27.2% (n = 94) in the low OxLDL group and 25.4% (n = 87) in the high OxLDL group (OR .92, 95% CI 0.68-1.23, P = .59). At 6-month angiography, restenosis was found in 28.1% of the patients (n = 74) in the low OxLDL group and in 24.2% of the patients (n = 61) in the high OxLDL group. (P = .31). CONCLUSION: Our study shows no association between circulating levels of OxLDL and restenosis or other adverse events in patients with coronary artery disease after coronary stenting.

Oxidized low density lipoproteins, statin therapy and severity of coronary artery disease.

BACKGROUND: The impact of statin therapy on the association between circulating levels of oxidized low density lipoproteins (OxLDL) and severity of coronary artery disease (CAD) has not been studied. METHODS: OxLDLs were measured in 687 patients with angiographically proven CAD (320 patients, 46.6% on statin therapy and 367 patients, 53.4% not on statin therapy on admission) using the Mercodia Oxidized LDL Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Patients on statin therapy had lower levels of OxLDL (median [interquartile range]; 63.9 U/L [53.9; 79.8] versus 72.3 U/L [58.4; 86.1], P<0.001) and C-reactive protein (3.0 mg/L [1.2; 6.6] versus 4.0 mg/L [1.7; 13.1], P<0.001) than patients not on statins. Multivariable analysis showed that statin therapy was an independent predictor of lower levels of OxLDL (P=0.0001). In univariate analysis, OxLDL level did not differ significantly among the patients with 1-, 2-or 3-vessel disease (70.5 U/L [57.5; 85.6], 66.3 U/L [53.8; 82.6] and 68.2 U/L [57.0; 83.4], respectively, P=0.26). Multivariable logistic regression analysis showed that OxLDL was an independent correlate of angiographic severity of CAD (P=0.04) and that there was an interaction (P=0.038) between statins and OxLDL in that the increased levels of OxLDL were associated with more extensive CAD. CONCLUSION: Patients with CAD who receive statins have lower levels of OxLDL and an attenuation of the relationship between circulating levels of OxLDL and CAD severity compared with patients who do not receive statins.

Plasma levels of N-terminal pro-brain natriuretic peptide in patients with coronary artery disease and relation to clinical presentation, angiographic severity, and left ventricular ejection fraction.

Comparative assessment of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) across a wide spectrum of angiographic and clinical coronary artery disease (CAD) in a consecutive series of patients has not been reported. This study examined 879 subjects (684 patients who had angiographically proved CAD and 195 controls who did not have CAD). NT-pro-BNP concentrations were measured before an angiographic procedure that allowed diagnosis of CAD and measurements of left ventricular ejection fraction and end-diastolic blood pressure. Median values (25th and 75th percentiles) of NT-pro-BNP in patients and controls were 474.5 pg/ml (162.3 and 1,542.8) and 117.0 pg/ml (60.1 and 230.6), respectively (p <0.001). In patients who had stable angina, unstable angina, and acute myocardial infarction, NT-pro-BNP concentrations were 327.7 pg/ml (129.2 and 973.2), 660.6 pg/ml (201.2 and 1,563.5), and 1,045.0 pg/ml (323.8 and 2,486.0, p <0.001). NT-pro-BNP concentrations in subgroups with 1-, 2-, and 3-vessel CAD were 385.5 pg/ml (117.2 and 1,266.0), 463.0 pg/ml (135.0 and 1,480.5), and 533.8 pg/ml (221.8 and 1,809.4), respectively (p = 0.005). Multivariable analysis showed that NT-pro-BNP was an independent correlate of the presence of CAD (chi-square 10.8, odds ratio 1.08, 95% confidence interval 1.03 to 1.13 for 100-pg/ml increase in concentration; p <0.001), acute coronary syndromes (chi-square 6.3, odds ratio 1.01, 95% confidence interval 1.00 to 1.02 for 100-pg/ml increase in concentration, p = 0.01) and a strong trend that was independently associated with angiographic severity (chi-square 3.68, p = 0.055). This study shows that NT-pro-BNP concentrations are high across the entire spectrum of CAD and parallel the clinical or angiographic severity of CAD.

Value of serum ferritin and soluble transferrin receptor for prediction of coronary artery disease and its clinical presentations.

We investigated whether there is an association between serum ferritin or soluble transferrin receptor (sTfR) concentrations and coronary artery disease (CAD) or its clinical presentations. This is a case-control study that included 892 patients (664 cases with angiographically proven CAD and 228 controls without CAD). Blood was collected before angiography for determination of sTfR, ferritin and C-reactive protein (CRP). The values (median, 25th-75th percentiles) of sTfR (2.6 [2.1; 3.2]mg/l versus 2.4 [2.1; 3.0]mg/l, P = 0.13) or ferritin (140.1 [74.8; 248.3]ng/ml versus 120.1 [74.9; 218.0]ng/ml, P = 0.11) did not differ significantly between cases or controls. The values of sTfR in the case subjects with 1-vessel, 2-vessel, and 3-vessel CAD were: 2.4 [2.0; 3.0], 2.6 [2.0; 3.2], and 2.8 [2.2; 3.3]mg/l, respectively (P = 0.003). In multivariate analysis, neither sTfR (chi2 = 0.14, P = 0.70) nor ferritin (chi2 = 2.8, P = 0.09) correlated independently with the presence of CAD. In case subjects with stable angina, unstable angina, and acute myocardial infarction (MI), ferritin concentrations were: 127.5 [69.5; 214.0], 138.9 [86.1; 278.0], and 175.0 [93.5; 314.5]ng/ml, respectively (P < 0.001). Our results showed that serum concentrations of sTfR or ferritin do not predict the risk for coronary artery disease. In subjects with pre-existing CAD, those with more severe disease had increased levels of sTfR. Patients with CAD presenting with acute coronary syndromes showed increased levels of serum ferritin.

Pharmacokinetics of vanadium in humans after intravenous administration of a vanadium containing albumin solution.

AIMS: Vanadium is currently undergoing clinical trials as an oral drug in patients with noninsulin-dependent diabetes mellitus. Furthermore, vanadium occurs in elevated concentrations in the blood of patients receiving intravenous albumin solutions containing large amounts of the metal ion as an impurity. The present study was performed to examine the pharmacokinetics of vanadium in humans following a single intravenous (i.v.) dose of a commercial albumin solution containing a high amount of vanadium. METHODS: The study was conducted in five healthy volunteer subjects who received intravenously 90 ml of a commercial 20% albumin infusion solution containing 47.6 micro g vanadium as an impurity. Vanadium concentrations in serum and urine were determined by electrothermal atomic absorption spectrometry. RESULTS: Vanadium serum concentrations after i.v. administration were measured for 31 days. The data could be fitted by a triexponential function corresponding formally to a three-compartment model. There was an initial rapid decrease in serum concentrations with half-lives of 1.2 and 26 h. This was followed by a long-terminal half-life time of 10 days. The terminal phase accounted for about 80% of the total area under the serum concentration-time curve (AUC). The mean apparent volume of distribution of the central compartment was found to be 10 l. The volume of distribution at steady state was 54 l, and total clearance was 0.15 l h(-1). Vanadium was mainly excreted by the kidneys. About 52% of the dose was recovered in the urine after 12 days. CONCLUSIONS: This study provides data on vanadium pharmacokinetics in healthy humans.

Binding of vanadate to human albumin in infusion solutions, to proteins in human fresh frozen plasma, and to transferrin.

The binding of vanadate (V) to human serum albumin (HSA) in infusion solutions, to human fresh frozen plasma (FFP), and to human transferrin (TF) was investigated over a wide concentration range. Free V concentrations were obtained by ultrafiltration. Total and free V concentrations were determined using electrothermal atomic absorption spectrometry (ETAAS). Binding parameters were obtained by non-linear regression. V only bound appreciably to HSA at low concentrations (<1 microM). The binding capacity of HSA was about 1000-fold lower than that of FFP and TF per mole of protein. Binding to FFP and TF in the concentration range investigated could be described by a combination of saturable and additional non-saturable binding. The respective maximal binding capacities (B(max), microM), dissociation constants (k(D), microM), and proportionality constants (C) for the non-saturable, linear binding were B(max)=27, k(D)=2.5, C=0.19 for FFP and B(max)=47, k(D)=0.47, C=0.38 for TF. The results suggest that V is predominantly bound to transferrin in FFP. It is concluded that HSA in infusion solutions represents a reservoir of readily accessible V. Nevertheless, given the high binding capacity of transferrin in plasma, the amount of vanadate delivered via the brief administration of HSA solutions is unlikely to be of major importance.