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Biomedical subjects

W Prellwitz

Publications and source records attributed to W Prellwitz.

At least 37 records · Page 2Linked to original sources

[Value of the CA 19-9 tumor marker in differential diagnosis of space-occupying lesions in the head of the pancreas].

In 96 patients (ductal pancreatic carcinoma, n = 34; periampullary carcinoma, n = 43; chronic pancreatitis, n = 19) the role of CA 19-9 in the diagnosis of lesions of the head of the pancreas were evaluated. The sensitivity for ductal pancreatic carcinoma was 73.3%, for periampullary carcinoma 48.8%, and specificity was 63.2%. Carcinoembryonic antigen was elevated only in every fifth patient. Even when combining the two tumor markers no increase in sensitivity could be observed. The low specificity of 63%, which decreased to 33% in the case of obstructive jaundice, does not allow adequate preoperative differentiation between cancer patients and those with chronic pancreatitis. In cases of postoperatively elevated CA 19-9 level the prognosis is worse than in patients with normal tumor markers.

Adult

Growth hormone substitution in growth hormone-deficient adults: effects on collagen type I synthesis and skin thickness.

Growth hormone stimulates collagen type I synthesis. Collagen type I is a common matrix compound in a large number of connective tissues. The aim of our study was to prove whether a stimulation of collagen type I synthesis might be accompanied by a deposition of collagen type I in the skin (cutis). Twenty growth hormone-deficient hypopituitary patients were included in a randomised, double-blind, placebo controlled, prospective, twelve-month study (eighteen patients assessable at the end of the study). The patients were treated with recombinant human growth hormone 0.25 U/kg/week subdivided in daily subcutaneous injections beginning with half the dosage during the first four weeks. During the first six months half of the patients were treated with placebo. PICP, the indicator of collagen type I synthesis, was increased after six months of therapy when compared to placebo. Skin thickness measured by ultrasound at the forearm and mechanically at the dorsum of the hand with strong compression of the skin both increased significantly following growth hormone substitution. Our data indicate that the stimulation of collagen type I synthesis by growth hormone substitution is followed by a deposition of collagen type I in the skin.

Adult

Recombinant hirudin as a periprocedural antithrombotic in coronary angioplasty for unstable angina pectoris.

Percutaneous transluminal coronary angioplasty is often complicated by thrombotic abrupt vessel closure in patients with unstable angina pectoris. The present multicentre trial was performed to determine the feasibility of two-dose regimens of recombinant hirudin (r-hirudin) compared to standard heparin in patients undergoing coronary angioplasty for unstable angina, and to investigate the effects of the different treatment regimen on markers of coagulation activation. At five participating centres, 61 patients were randomly enrolled in one of two sequential groups of r-hirudin (group 1: 0.3 mg.kg-1 i.v. bolus, 0.12 mg.kg-1.h-1 i.v. infusion; 21 patients; group 2: 0.5 mg.kg-1 i.v. bolus, 0.24 mg.kg-1.h-1 i.v. infusion; 19 patients) or in a heparin control group (150 IU.kg-1 i.v. bolus, 20 IU.kg-1.h-1 i.v. infusion; 21 patients). Antithrombotic therapy was started immediately before coronary angioplasty and continued for 24 h. This was followed by a low-dose anticoagulant infusion for another 24 h (r-hirudin: 0.04 mg . kg-1 . h-1; heparin: 7 IU . kg-1 . h-1). Activated partial thromboplastin time, r-hirudin plasma concentrations by both immunological and functional assay, thrombin-hirudin complex, thrombin-antithrombin III complex, soluble fibrin, and prothrombin fragment 1 + 2 were closely monitored. The median partial thromboplastin time prolongations at 24 h vs baseline were found to be 1.9-fold and 2.3-fold in r-hirudin group 1 and dose group 2, respectively, and 3.0-fold in the heparin group. There was a dose-dependent correlation between partial thromboplastin time and the r-hirudin plasma levels (r = 0.61). In five of 21 patients of dose group 1, three of 19 patients of dose group 2, and 10/21 patients of the heparin group, partial thromboplastin time values exceeding the predefined target range prompted an interruption of the infusion. One major bleeding complication occurred in dose group 2. The functional assay for the estimation of r-hirudin plasma concentrations showed excellent correlations to the immunological technique (r = 0.99). Differences between the thrombin-hirudin complex levels could not be observed. Increased concentrations of thrombin-antithrombin III complex, soluble fibrin, and prothrombin fragment 1 + 2 were seen 4-8 h after coronary angioplasty and after reduction of the high-dose therapy in dose group 1 when compared with dose group 2 and the heparin group, respectively. Based on coagulation tests the present study showed the feasibility of a periprocedural antithrombotic regimen with r-hirudin for patients undergoing coronary angioplasty for unstable angina. In addition to the partial thromboplastin time the determination of r-hirudin plasma levels by a chromogenic substrate assay considerably improves the monitoring of therapy. The lower dose r-hirudin regimen seems to be suboptimal as periprocedural anticoagulation in coronary angioplasty patients as indicated by markers of thrombin generation and thrombin activity.

Adult

Increased plasma concentration of fibrin monomer in acute myocardial infarction with early reperfusion.

OBJECTIVE: To assess whether plasma fibrin monomer (FM) concentration, a marker of thrombin activity, is increased in the first hours after acute coronary occlusion and whether there are differences between patients with and without early reperfusion. DESIGN: Thirty-five consecutive patients with acute myocardial infarction (AMI) and early coronary angiography were studied prospectively. METHODS: Plasma FM samples taken on admission (< 6 h after onset of chest pain) and 6-14 h after onset of chest pain were analysed using a specific enzyme immunoassay. All of the patients were anticoagulated with heparin intravenously. RESULTS: Of the 35 patients, 28 had angiographically documented reperfusion within the first 6 h, whereas seven patients had no early reperfusion. FM concentrations were measured in the reference range (< or = 3.6 mg/l) within the first 6 h in 32 of the 35 patients. At 6-14 h FM concentrations were elevated in the reperfusion group (median 4.56 mg/l), but not in the group without reperfusion (median 1.6 mg/l, P = 0.0063). Using a threshold value of 3.0 mg/l, sensitivity and specificity of FM for the non-invasive recognition of early reperfusion were 78 and 83%, respectively. The specificity was similar to that for troponin T and higher than the creatinine kinase MB specificity. CONCLUSIONS: FM plasma concentrations are elevated in patients with AMI and early reperfusion. With a single blood sample 6-14 h after onset of chest pain, FM analysis is useful for the non-invasive detection of early reperfusion after AMI.

Anticoagulants

Evaluation of an automated chromogenic substrate assay for the rapid determination of hirudin in plasma.

A fully mechanized chromogenic substrate assay method for the rapid and specific determination of recombinant hirudin (r-hirudin) in citrated plasma on clinical chemistry analyzers (Hitachi 911 and Cobas Mira) is described. In a first step, 12 microliters sample volume is mixed with the chromogenic substrate. Due to the almost immediate action of hirudin the inhibitory reaction and the cleavage of the substrate is started simultaneously when bovine thrombin is added in excess. This excludes interferences by antithrombin III or heparin cofactor II. The change in absorbance/min is recorded at 405 nm. The measuring range is about 0.2-4.0 mg/l r-hirudin on both analyzers. Precision is characterized by intraassay coefficients of variation between 0.63% and 2.78% on the Hitachi 911 and 1.51% and 7.84% on the Cobas Mira, respectively and interassay coefficients of variation of 3.57% to 9.15% (Hitachi 911) and 3.72% to 12.99% (Cobas Mira) for the same r-hirudin plasma concentrations. The described determination of r-hirudin correlates well with an enzyme linked immunosorbent assay method for r-hirudin (Hitachi 911: r = 0.964, y = 0.978x + 0.038, n = 323; Cobas Mira: r = 0.964, y = 0.959x-0.003, n = 323).

Animals

Biochemical bone markers compared with bone density measurement by dual energy X-ray absorptiometry.

In contrast to medical imaging, the biochemical markers allow a more frequent determination and are not as invasive as histomorphometric methods. We investigated biochemical markers of type I collagen compared with bone density measurements in 85 females between 41 and 89 years of age (median: 57 years). The bone density measurements were performed by dual energy X-ray absorptiometry (DXA) on the lumbar spine (L1-4). The bone density measurements were stated as a percentage of the norm. All patients were divided into three groups: I = <80%; II = 80-130%; III = >120%. Based on this classification the median concentration of the I-carboxyterminal propeptide of type I collagen in serum (S-PICP) as an anabolic marker of type-I collagen increased significantly with rising bone density: I 65.0 micrograms/liter (interquartile range: 52.1-78.0 micrograms/liter); II 85.9 micrograms/liter (52.1-115.5 micrograms/liter); III 81.4 micrograms/liter (62.0-101.0 micrograms/liter);P < 0.05. The concentration of urinary pyridinolines (U-PYR) as a marker for degradation of type I collagen decreased. The I-carboxyterminal telopeptide (S-ICTP) and osteocalcin (S-BGP) did not change. The multivariate regression analysis showed no relationship between between bone density and biochemical bone markers. Only the age significantly correlated negatively with bone density measurement. For a better assessment of type I collagen metabolism we created a "b-quotient" by dividing the sum of S-PICP and S-BGP by U-PYR. The median b-quotient increased significantly: I 1.55 (0.97-2.04); II 2.09 (1.57-2.86): III 2.46 (1.58-3.22); P < 0.05. Changes in bone metabolism cannot be identified by the determination of a single marker. However, the improved biochemical diagnostic measurement using the b-quotient may provide early information about the progression of a metabolic disorder within the interval of imaging.

Absorptiometry, Photon

Guidance of anticoagulation after intracoronary implantation of Palmaz-Schatz stents by monitoring prothrombin and prothrombin fragment 1 + 2.

The primary objective of this study was to apply a sophisticated coagulation monitoring system including estimation of the concentration of prothrombin fragment 1 + 2 (PTF 1 + 2) and the activity of prothrombin (coagulation factor II or FII) to cases of stent implantation and to compare the results with those of standard coagulation tests. The secondary objective was to detect the incidence after stenting of subacute thrombosis (SAT) and bleeding complications in these patients and to compare the results with those of a group of patients with stent implantation in whom coagulation was monitored exclusively by standard tests. SAT several days after coronary stenting occurs in up to 20% despite aggressive intravenous and overlapping oral anticoagulation. According to a prospective study protocol 120 consecutive patients with implantation of 155 Palmaz-Schatz stents underwent coagulation monitoring including single daily estimation of the concentration of PTF1 + 2 (target range < 0.5 nmol/L) and of FII activity (15% to 35%) in addition to the standard tests of thrombin time (TT), partial thromboplastin time (aPTT), international normalized ratio (INR), antithrombin III (ATIII), and fibrinogen. Adjustment of heparin and phenprocoumon dosages in this study group was based only on the results of PTF1 + 2 and FII measurements. A control group consisted of 53 patients with implantation of 64 stents who were matched for baseline, angiographic, and procedure-related characteristics. After stenting, anticoagulation was monitored by estimation of TT (target range > 70 seconds), aPTT (> 70 seconds), INR (3.0 to 4.5), AT III (> 80%), and fibrinogen (< 450 mg/dl) in this control group. There was a weak correlation between PTF1 + 2 and aPTT (r = 0.337; PTF1 + 2 = -0.00169aPTT + 0.491) and PTF1 + 2 and TT (r = 0.328; PTF1 + 2 = -0.00142TT + 0.494). A better correlation was found between FII and INR (r = 0.983; FII = -23.8 INR + 134). Stable oral anticoagulation was maintained 2.8 +/- 0.9 days later according to an FII concentration of < 35% compared with an INR > 3. The incidence of SAT was 3.3% with 3.0% for elective versus 3.8% for nonelective stenting. The sensitivity, specificity, and accuracy of the PTF1 + 2 test were 100%, 88%, and 88%, respectively. In the control group the incidence of SAT was 17%, with 16.1% for elective versus 18% for nonelective stenting. Major bleeding complications occurred in 10% (study group) and in 11.3% (control group) of patients (no statistical difference).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Recombinant hirudin (HBW 023) prevents troponin T release after coronary angioplasty in patients with unstable angina.

OBJECTIVES: This study was performed to evaluate the efficacy of peri-interventional treatment with recombinant hirudin (r-hirudin [HBW 023]) compared with heparin in the prevention of troponin T release in patients with unstable angina. BACKGROUND: Percutaneous transluminal coronary angioplasty in patients with unstable angina is associated with a high risk of acute thrombotic complications. METHODS: Serial troponin T measurements were performed in 61 patients with unstable angina during the 48-h observation period after coronary angioplasty of the ischemia-related lesion. Patients were randomly assigned to peri-interventional intravenous treatment with either r-hirudin (dosage group I: 0.3-mg/kg body weight bolus, 0.12 mg/kg per h for 24 h; dosage group II: 0.5-mg/kg bolus, 0.24 mg/kg per h for 24 h) or heparin (150-IU/kg bolus, 20 IU/kg per h for 24 h). All patients received acetylsalicylic acid before coronary angiography. After 24 h, patients received a constant low dose infusion of either hirudin (0.04 mg/kg per h) or heparin (7 IU/kg per h) for another 24 h. The power of the study to detect a decrease in abnormal troponin T levels from 60% (heparin group) to 20% (combined r-hirudin groups) was 88%. RESULTS: Serial troponin T measurements revealed two peaks within the 48 h after coronary angioplasty in the heparin but not the hirudin groups. An elevated serum troponin T concentration (> 0.2 ng/ml) within 48 h of coronary angioplasty was found in 9 (24%) of 38 patients in the hirudin groups (5 [25%] of 20 in dosage group I; 4 [22%] of 18 in dosage group II) compared with 11 (58%) of 19 in the heparin group (p = 0.01). We observed major cardiac events (death, myocardial infarction, abrupt vessel closure) in 1 (4.8%) of 21 patients in dosage group I, 1 (5.3%) of 19 in dosage group II and 3 (14.3%) of 21 in the heparin group (p = 0.33). CONCLUSIONS: In this pilot trial, hirudin appears to be superior to heparin in preventing troponin T release after coronary angioplasty.

Angina, Unstable

[The use of low-molecular heparin for anticoagulation in pregnancy].

A 26-year-old woman, on bedrest since the 6th week of pregnancy because of threatened abortion, developed thrombosis in the left iliac, superficial femoral and common femoral veins with small pulmonary emboli in the 11th week. Inhibitor deficiency was excluded. The thrombosis was only partially recanalized by unfractionated heparin at therapeutic dosage (38,400 IU per 24 h). As thrombolysis treatment and oral anticoagulation were contraindicated because of the threatened abortion, coagulation with low molecular weight heparin (LMWH) was started in the 18th week (5000 anti-Xa units daily subcutaneously). Maximal anti-Xa activity in plasma never exceeded 0.3 U/ml and there were no complications. The patient was delivered of a healthy girl (2,660 g, 48 cm) by caesarean section in the 37th week. Immediately post-partum LMWH was demonstrated with an anti-Xa activity of 0.3 U/ml in maternal blood, but none in simultaneously obtained cord venous blood. This case suggests that treatment of phlebothrombosis with LMWH is a reasonable measure even during pregnancy.

Abortion, Threatened

Laboratory control of minimal heparinization during haemodialysis in patients with a risk of haemorrhage.

For patients undergoing dialysis with a high risk of haemorrhage there is no standardized procedure for anticoagulation during extracorporeal circulation. Minimal heparinization with a dose equivalent to half that used for chronic haemodialysis was employed in 49 patients (125 haemodialyses) performed after operative interventions (83.3%), after haemorrhagic events (5.2%) and after invasive investigations (11.5%). Using a biocompatible membrane and a low molecular weight heparin (bolus dose 500-1300 U; continuous infusion 100-400 U) it was possible to complete haemodialysis in 74 cases (Group 0) without clots appearing in the venous bubble trap of the tubing system. In 30 cases (Group 1) only small clots were detected at the end of haemodialysis, and in 13 cases (Group 2) larger clots (exceeding a diameter of 1 cm) were found. In eight cases (Group 3) partial or complete clot formation occurred in the tubing. No haemorrhagic complications were observed. Anti-Xa activity, thrombin-antithrombin III complex (TAT) and D-dimer were determined before haemodialysis, 2 h after the start of haemodialysis and on completion of the procedure. The anti-Xa activities ranged between < 0.2 and 0.56 U/ml. In contrast, at 2 h there were significant differences (P < 0.05) in the TAT concentrations between Group 0 and the other groups, as well as between Group 1 and Group 2 and 3. Significant differences (P < 0.05) in D-dimer levels occurred only at the end of haemodialysis. Minimal heparinization in haemodialysis is a practicable alternative in patients with a high risk of haemorrhage and extended coagulation monitoring is helpful in adjusting heparin dosage.

Adult

The phenomenon of a high triglyceride response to an oral lipid load in healthy subjects and its link to the metabolic syndrome.

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.

Adult

Immunonephelometric determination of the C4b-binding protein.

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.

Administration, Oral

Influence of blood sampling from venipunctures and catheter systems on serial determinations of prothrombin activation fragment 1 + 2 and thrombin-antithrombin III complex.

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)

Antithrombin III

[Prevention of thrombosis in protein C deficiency].

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.

Adolescent

[Multicenter results of coronary implantation of balloon expandable Palmaz-Schatz vascular stents].

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%.

Adult