Cardiac troponins in serum in chronic renal failure.
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Biomedical subjects
Publications and source records attributed to W Prellwitz.
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Excessive postprandial triglyceride (TG) responses despite normal fasting TG levels have been described in single cases within small groups of healthy subjects and in patients with obesity or precocious atherosclerosis, known to be associated with high insulin fasting levels. To clarify this association, fasting and postprandial TG and insulin levels were studied in 113 healthy young (25.7 +/- 2.6 years), normal weight (body mass index 20.8 +/- 2.3 kg/m2) male subjects who were selected from among 117 subjects on the basis of TG fasting levels < 200 mg/dl. After a 12-hour fast a standardized liquid lipid load was administered containing 58 g mainly saturated fat and 1,017 kcal energy. Both fasting TG values and postprandial TG peak values showed bimodal frequency distributions. Statistical analysis of fasting TG discriminated two groups: a low fasting TG group with normally distributed values < 150 mg/dl (mean +/- SEM: 79.5 +/- 2.7 mg/dl; n = 104) and a high fasting TG group > 150 mg/dl (194.5 +/- 7.2 mg/dl; n = 13). Likewise, two groups could be differentiated according to their maximal postprandial TG response (TG max) to the lipid load: (1) normal responders with TG max < 260 mg/dl (mean +/- SEM: 123 +/- 4.8 mg/dl; n = 96) and (2) high responders with TG max > 260 mg/dl (272.5 +/- 20.5 mg/dl; n = 17). Fasting TG and TG max were highly correlated (r = 0.745; p < 0.0001). However, 9 of 17 (53%) high responders had fasting TG < 150 mg/dl, which means that the prediction of high response is only 47.0% based on fasting TG values. Fasting insulin levels were significantly higher in high responders than in normal responders, whereas they did not differ between the low and high fasting TG group. In conclusion, the bimodal frequency distribution of TG max after a lipid load permitted the differentiation of two groups, normal responders and high responders, with higher fasting insulin levels, which might indicate a link to the metabolic syndrome.
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A fully mechanised immunonephelometric method for the rapid and specific determination of C4b-binding protein (C4b-BP) in citrated plasma is described. The method utilizes commercially available rabbit antiserum against human C4b-BP and a nephelometer analyser. A single determination can be performed within 6 min, requiring 80 microliters sample volume. The measuring range is about 10 to 200% of normal C4b-BP. Precision is characterized by intraassay coefficients of variation between 1.5% and 2.8%, and interassay coefficients of variation between 4.0% and 4.6% for the same C4b-BP concentrations. The nephelometry of C4b-BP was correlated with electroimmunodiffusion (Laurell technique; r = 0.863, y = 0.909x+7.091, n = 79). C4b-BP concentrations (143%, 96-223%; median and 2.5th-97.5th percentile) from 83 subjects with increased inflammation markers C-reactive protein (> 10 mg/l), and fibrinogen (> 4.5 g/l) showing significantly higher C4b-BP concentrations compared to 151 obviously healthy subjects (97%, 68-141%; p < 0.001). In contrast to 81 patients with therapeutic heparinisation (90%, 60-131%) significant decreased concentrations were found in 90 subjects under oral anticoagulant therapy (OAT) in the stable state (78%, 44-125%; p < 0.001). Depending on different INR levels (< 2.5, n = 40: 71%, 63-85%; > 2.5, n = 50: 81%, 68-92%; median and 25th-75th percentile) no significant differences of C4b-BP concentrations could be measured.
To evaluate the influence of different blood sampling techniques on test results of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (F1 + 2) serial determinations were performed. In six groups of nonrandomized patients (ten patients each) the concentrations of the coagulation markers of blood samples from central catheters (internal jugular, caval, Shaldon, pulmonary artery) and peripheral cannulas (17G and 18G) were compared with those of blood samples obtained simultaneously from direct venipunctures of the contralateral arm. Medians and 25th-75th percentiles of TAT and F1 + 2 concentrations of plasmas obtained from central catheters were not different from those taken from venipunctures. When delta mean values (catheter - venipuncture) were calculated negative results were obtained, indicating lower concentrations measured from blood sampled through central catheters with the exception of blood that taken from Shaldon catheters. Only for TAT concentrations significantly were lower values measured in blood samples taken from internal jugular catheters when compared with blood samples obtained from direct venipunctures. Significantly higher TAT concentrations were determined in blood samples obtained from Shaldon catheters. For both coagulation markers correlations were found between concentrations in blood samples from central catheters and venipunctures. In blood samples taken from peripheral venous cannulas only F1 + 2 concentrations correlated with the concentrations found in samples from direct venipuncture. In contrast to F1 + 2, TAT concentrations measured from blood samples via peripheral cannulas were determined significantly higher than those taken from direct venipunctures.(ABSTRACT TRUNCATED AT 250 WORDS)
In a 14-years old girl, suffering from deep venous thrombosis protein C deficiency (activity: 55-58%) was diagnosed. Following rethrombosis oral anticoagulant therapy (OAT) with Phenprocoumon (Marcumar) was started. To find the required dosage for OAT the concentrations of prothrombin fragment (F1+2; < 0.5 nM/l) and fibrin monomers (< 2.5 mg/l) were measured. With this procedure an unusually high thromboplastin time (40-45%) was found to be safe.
Intracoronary stenting was designed to handle acute vessel closure after balloon angioplasty and to reduce the rate of restenosis. In three cardiology centers the implantation of 200 balloon-expandable Palmaz-Schatz stents was attempted in 179 patients. The implantation was successful in 170 patients (95%). During bail-out implantation for acute vessel closure or symptomatic dissections after balloon angioplasty, implantation succeeded in 60 (91%) of 66 attempted patients, who recovered immediately from ischemia. Three patients received emergency bypass surgery and three patients were kept on medical therapy. Restenosis after 4 to 6 months, defined as > 50% diameter reduction, was documented angiographically in 18 (15.3%) of 118 presently controlled patients. Patients with single stent implantation (n = 106) presented a late restenosis rate of 10.4% in contrast to patients with multiple stent implantation (n = 12), who presented a restenosis rate of 58.4%. Similar results on restenosis were found for patients with elective and bail-out stent implantation. Acute thrombotic stent occlusion occurred in three patients (1.8%) during the first 24 h after stenting. Three to 9 days after implantation subacute stent thrombosis occurred in 15 (8.8%) of 170 patients. Despite adequate therapy including thrombolysis, balloon angioplasty or emergency bypass surgery in 14 of 15 patients Q-wave myocardial infarction was documented in six patients and non Q-wave myocardial infarction in five patients. The following parameters were identified as risk factors for the development of subacute stent thrombosis: bail-out indication, unstable angina, type C lesion, stenosis length > 1.5 cm, plaque area > 3.5 mm2, symptomatic dissection after balloon angioplasty, incomplete wrapping of the dissection after stenting and residual distal vessel irregularities after stenting. Bleeding complications occurred in 12.4% of the patients and were related to the anticoagulation and antiaggregation therapy. In conclusion, the implantation of Palmaz-Schatz stents is an excellent bail-out device to treat acute vessel closure or symptomatic dissections after angioplasty. Elective and bail-out single stent implantation is associated with a reduced rate of restenosis when compared to conventional balloon angioplasty. At present, subacute stent thrombosis and bleeding complications are the major limitations with a combined rate of 15.9%.
A test kit (Iso-ALP, Boehringer Mannheim) for measuring human bone alkaline phosphatase activity in serum or plasma was evaluated in five laboratories in three countries. The assay is based on the principle described by Rosalki and Foo (Clin Chem 1984;30:1182-6) and uses wheat germ lectin to precipitate bone alkaline phosphatase. Residual ALP in the supernate in comparison with total ALP is used to quantify the bone fraction. The imprecision of residual ALP measurement was low (median between-run CV 4.9%) and comparable with that of total ALP. Linearity of precipitation was demonstrable up to a bone ALP activity (diethanolamine buffer 37 degrees C) of 2000 U/L, though a matrix effect was observed for dilutions of high-activity sera in saline or bovine serum albumin. For assaying patients' samples, different batches of lectin demonstrated excellent comparability. Taking electrophoresis as a basis for standardization, we determined that the lectin precipitated approximately 90% of bone ALP, but < 5% of nonbone ALP. From this we derived serum/plasma upper reference limits for bone ALP activity in adults and children.
Patients with intracoronary stent implantation are treated with aggressive anticoagulant and antiplatelet therapy consisting of high-dose heparin, phenprocoumon, acetylsalicylic acid, dipyridamole, and the infusion of dextran to prevent a subacute thrombotic occlusion of the stented segment. In an effort to optimize this treatment by reducing both imminent bleeding complications and subacute thrombotic occlusion, the concentrations of prothrombin fragment 1 + 2 (F 1 + 2) were determined after intracoronary Palmaz-Schatz stent implantation in 19 consecutive patients. The F 1 + 2 concentrations after stent implantation and before the initiation of oral anticoagulant therapy (OAT) were 0.35 nm/l and 0.25-0.53 nm/l (median and 25th-75th percentile), versus 0.74 nm/l and 0.52-0.78 nm/l, in healthy subjects and 0.61 nm/l and 0.30-1.02 nm/l in 15 patients with ongoing proximal DVT. Nine days after initiation of OAT, F 1 + 2 concentrations in both patient groups had not yet reached levels observed in patients with OAT in the stable state (0.16 nm/l, 0.12-0.26 nm/l; n = 76; P less than 0.0001 compared with healthy subjects; INR 2.0-4.5). Despite an INR greater than 2.0, accompanying heparinization was terminated on day 9. In two stented patients a minor bleeding complication arose after the removal of the arterial catheter. Subacute thrombotic occlusions were not observed. Since F 1 + 2 concentrations did not exceed the upper limit of normal range (1.11 nm/l) in any of the 19 patients, the therapeutic regimen was not changed. Monitoring F 1 + 2 may thus be helpful in introducing a more individual treatment if aggressive anticoagulation has to be performed.
In seven patients who had to be dialysed between four and 13 times due to acute renal failure, low molecular weight heparin (LMWH) Fragmin was used for anticoagulation. According to dose-finding studies, 80-90 U kg-1 body weight of LMWH as a single bolus were administered initially, producing dose-related levels of 0.3-1.5 anti-factor Xa U ml-1 in plasma. Apart from the anti-Xa activity in the plasma, the thrombin anti-thrombin III complex (TAT complex) and a fibrin degradation product (D-dimer) were measured as parameters of a coagulation activation. A sufficient anti-coagulation during dialysis was supposed to exist at a normal range (5.0 micrograms l-1 or below) of TAT complex. Pathological TAT concentrations at the end of dialysis indicated the requirement of an increased dose for the next dialysis. These concentrations reflected a need for more heparin if, for example, inflammation, indicated by increasing C-reactive protein levels (CRP), occurred. The increase of TAT complex and D-dimer during dialysis showed a good agreement (p less than 0.001). Due to a single bolus application before dialysis, one measurement of TAT at the end of the dialysis was sufficient. The determination of the TAT complex concentration enabled a heparinization better adapted to the clinical situation of intensive-care patients undergoing acute dialyses, so that the coagulation system was not additionally activated by the extracorporeal circulation.
In 13 healthy, male nonsmokers (mean age: 25.7 +/- 2.4 years) with normal fasting triglycerides we investigated postprandial changes of triglycerides in several lipoprotein fractions. After a 12-hour overnight fast they ingested a standardized lipid load (1,017 kcal) including 30,000 IU retinyl palmitate. Postprandially, total triglycerides increased significantly (p < 0.001) to a peak value of 221 +/- 81 mg/dl at 5 h. Two subjects had an exceptionally strong triglyceride response (peak values: 363 and 390 mg/dl). They had the highest levels of retinyl palmitate in the chylomicron and the nonchylomicron fraction, and one of them showed elevated intermediate-density lipoprotein values throughout the test period. In addition, they showed an altered early and an increased late postprandial insulin response. Thus, our data provide evidence that an exaggerated postprandial triglyceride response may point to an increased atherogenic risk even in healthy subjects with normal fasting triglycerides.
Postperfusion syndrome is still a problem in long cardiac operations using extracorporeal circulation (ECC). To evaluate whether or not centrifugal blood pumping during open heart surgery is beneficial, a randomized, prospective study was undertaken of 50 consecutive patients undergoing elective coronary artery bypass grafting. The patients were divided into two groups of 25 each. In group 1 a centrifugal pump (Biomedicus) was used as arterial blood pump, while in group 2 a roller pump (Stöckert) was used. The two groups did not differ significantly and the number of variables during surgery was kept low (identical perfusion set, two surgeons, minimal cardiotomy suction). The parameters studied included the cellular elements of the blood and components indicating their functional integrity, such as PMN-elastase, plasma hemoglobin, beta-thromboglobulin, and thrombin-antithrombin III complex and D-dimer as representatives for activated coagulation and secondary fibrinolysis. Blood and urine samples were taken every 15 min during ECC, on arrival in the intensive care unit, and 1, 3, 6, 12, and 24 h thereafter. No difference between the groups was found in regard to bypass time, ECC flow and volume, fluid balance, and clinical outcome. Significant differences in favor of group 1 were found in plasma hemoglobin (P less than 0.05), beta-thromboglobulin (P less than 0.01), D-dimer (P less than 0.05), and platelet counts (P less than 0.5). These differences were clearly ECC-time-dependent and became statistically significant after 90 min bypass. We conclude that roller pumps still can be safely used for standard cardiac procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
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Despite the improvements in the development of dialyzer membranes with greater hemocompatibility, an activation of the coagulation system occurs when blood comes into contact with exogenous surfaces. The large number of heparin dosage regimens demonstrated the difficulty to adapt general therapeutic guidelines. Low molecular weight heparin (Fragmin) was administered as a single bolus dose for anticoagulation during 58 acute dialyses. Anti-Xa-activity, the plasma levels of the lysosomal elastase of the polymorphonuclear granulocytes ("PMN-elastase") and of the thrombin-antithrombin III-complex (TAT) were measured at hourly intervals. Therapeutic anti-Xa-levels did not show evidence of sufficient inhibition of thrombin formation. The PMN-elastase increased by 180 ng/ml 3 h after administration of the bolus dose, with no further increase occurring (plateau phase). This was considered to reflect adequate anticoagulative activity. Where anticoagulation was inadequate, the elastase values rose consistently. After 2 h the increase of the PMN-elastase showed that--and to what extent--coagulation had been activated. The determination of PMN-elastase, using the IMAC-principle, is a method which can be performed quickly with any conventional autoanalyzer. It makes it possible to monitor adequate anticoagulation, but PMN-elastase results must be proven during routine use before recommendation as a routine test.
This paper describes a fully mechanized homogeneous immunoassay using the immunoactivation method for the rapid and specific determination of human granulocyte elastase (EC 3.4.21.37) in plasma. The method uses anti-elastase antibody fragments from sheep, conjugated to horseradish peroxidase. These enzyme-antibody conjugates bind to the elastase-alpha 1-proteinase inhibitor complex present in plasma. A separate sample blank with non-specific sheep antibody fragments conjugated to horseradish peroxidase corrects for errors introduced by the sample matrix. Measurements were performed with the clinical chemistry analyser Hitachi 717. A single determination can be performed in 10 min, requiring 24 microliters sample volume. The measuring range is about 20 to 1000 micrograms/l elastase. For within-run precision the coefficients of variation are 4.77%, 4.48% and 1.85% for elastase concentrations of 45.7, 89.1 and 385.4 micrograms/l; for day-to-day precision the coefficients of variation are 15.81%, 7.19% and 4.12% for elastase concentrations of 31.1, 65.5 and 440.2 micrograms/l, respectively. Correlation (y = bx + a) of results with those from the heterogeneous immunoassay showed a good agreement (r = 0.93, b = 1.11, a = -27.0, N = 121). Interferences by endogeneous substances and by drugs at therapeutic doses were not observed. The reference interval, determined by using plasma from 215 healthy individuals (C-reactive protein less than 5 mg/l, leukocyte count 4-8 x 10(9)/l), was 9-56 micrograms/l (2.5th to 97.5th percentile), with a median of 27 micrograms/l.
For humans, ecological and epidemiological results are reported that show a relationship between the serum selenium concentration and cardiovascular disease in populations where low serum selenium concentrations are found, e.g., in Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland, and Sweden, subnormal serum selenium and partially whole blood selenium concentrations are reported in patients with acute myocardial infarction. For patients with coronary arteriosclerosis, subnormal serum selenium concentrations are reported from the USA and Germany and subnormal whole blood selenium concentrations from Germany. Subnormal serum and subnormal whole blood selenium concentrations of patients with cardiomyopathy are reported from non Keshan disease affected areas in Germany, France, and China. In selenium deficiency, an accumulation of lipid peroxides in the heart may occur, especially under ischemic conditions and if ischemic tissue is reperfused. Lipid peroxides in the heart may damage the cell membrane and may lead to an impaired calcium transport with an uncontrolled calcium accumulation in the cell. This may result in an activation of phospholipids, and, in consequence, to an enhanced formation of arachidonic acid. An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxane, causing enhanced blood pressure and platelet aggregability. From animal experiments, it is known that selenium protects against cardiotoxic elements, cardiotoxic xenobiotics, and viral infections that affect the heart. Selenium deficiency may also be a secondary factor in the causation of hypertension and myocardial ischemia.
The excretion of selenium in urine was determined in West German healthy volunteers. Women excrete 17.7 +/- 4.2 micrograms Se/d and men 19.0 +/- 9.0 micrograms Se/d. The daily selenium excretion per gram creatinine is 13.5 +/- 3.8 micrograms Se/g crea for women and 9.8 +/- 3.3 micrograms Se/g crea for men. The clearance of selenium from the plasma is calculated with 0.18 mL/min. The selenium excretion per day is positively correlated with the 24 h excretion of urea and creatinine. The correlation of the selenium excretion with the urea excretion is most probably owing to the fact that the selenium intake of West Germans is linked primarily to foods with high protein contents. That the selenium excretion is directly correlated with the creatinine excretion is an indicator that the muscle, which accounts for nearly 50% of the whole body selenium in West German adults, influences the selenium excretion in urine. The positive correlation of the selenium excretion with the potassium excretion also indicates that the muscle mass contributes significantly to the selenium excretion in urine. Another indicator that the selenium excretion is influenced by the muscle is that after intensive muscular activity (running), selenium excretion is enhanced. The 24 h selenium excretion is dependent on the glomerular filtration rate of the kidney characterized by the creatinine clearance. This result is important, because if the selenium excretion is used as parameter for the selenium status of humans, the kidney function should be known. This is a limitation for the use of the urinary selenium excretion as parameter for the selenium status. This is especially important for patients whose glomerular filtration rate is low. The 24 h selenium excretion is further influenced by the 24 h urine volume. Selenium losses via urine may be concomitant with protein losses in urine.
Currently two major types of centrifugal pumps are commercially available for ventricular assist: the Biomedicus-cone (Group I) and the Centrimed-impeller pump (now Sarns 3M) (Group II). To compare them for blood trauma and hemolysis, an in-vitro experiment was designed with a Stöckert roller pump as a standard control (Group III). The in-vitro circuit was constructed consisting of a pump head, electromagnetic flow probe, polyvinyl chloride tubing and a reservoir, identical for all groups. Human ACD blood was used for priming and was circulated with a flow rate of 2 L/min for 24 h. Blood samples were taken at 0, 1, 3, 6, 12, and 24 h and zero control values were subtracted from the resulting data per time interval. Among the 16 parameters studied, a highly significant difference in favor of Group I was found for glutamate oxalacetate transaminase (GOT) and lactate dehydrogenase (p less than 0.0001) and for the free plasma hemoglobin (p less than 0.0001) after 12 and 24 h, respectively. The hemolytic index (Allen) again was lowest for group I in contrast to Groups II and III (0.012 versus 0.060 and 1.70) after 24 h. All other parameters studied did not render significant differences between the systems tested. The authors conclude that the Biomedicus pump currently is the least traumatic centrifugal pump for ventricular assist.