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M Heins

Publications and source records attributed to M Heins.

At least 19 recordsLinked to original sources

Plasma levels of D-dimer and circulating endothelial adhesion molecules in veno-occlusive disease of the liver following allogeneic bone marrow transplantation.

Veno-occlusive disease (VOD) of the liver is a frequent and life-threatening complication of BMT. Recently, successful treatment by t-PA has been reported but has been compromised by fatal bleeding events. Therefore, t-PA application should be restricted to patients with severe VOD. However, moderate and severe forms of VOD are difficult to distinguish in early stages. We analyzed plasma levels of cross-linked fibrin degradation products (D-dimer) and soluble endothelial adhesion molecules such as sE-selectin, sVCAM-1 and sICAM-1 in 10 consecutive patients undergoing allogeneic BMT to evaluate their use in identifying severe forms of VOD. During the observation period, 4 episodes of VOD occurred, 2 of which were fatal due to early onset of multiorgan failure. Concentrations of D-dimer generally increased after transplantation. However, there was an additional significant increase in D-dimer levels during severe VOD. Thus, D-dimer levels above 1000 microg/l were only found in 2 cases with severe VOD and fatal outcome. When compared with bilirubin concentrations substantial increases of D-dimers appeared earlier during the course of severe VOD. In contrast, VOD episodes were not accompanied by significant increases in sE-selectin, sVCAM-1 and sICAM-1 levels. It is concluded that measurement of D-dimer concentrations may aid accuracy to the early diagnosis of severe VOD.

Adult

Influence of time and temperature on coagulation analytes in stored plasma.

There is no comprehensive study on the stability of coagulation analytes in plasma. We therefore determined the influence of storage time and temperature on prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, factors V and VIII, antithrombin III, protein C and S in plasma from 20 healthy subjects and 20 patients receiving heparin therapy. The stability in plasma, defined as the period during which there was a change of less than 10% from the initial value, was 8 hours for activated partial thromboplastin time, 24 hours for prothrombin time, 48 hours for factor V and 7 days for thrombin time, fibrinogen, protein C and antithrombin III in healthy subjects at 6 degrees C. Factor VIII and protein S showed 19 and 12 % reduction in activity, respectively, after 8 hours. In volunteers not treated with heparin therapy, activated partial thromboplastin time was stable for 8 hours; prothrombin time for 48 hours; and thrombin time, fibrinogen and antithrombin III for 7 days with sample storage at room temperature. Factor VIII showed a decrease of 18 % after 8 hours. For patients receiving heparin therapy, the stability of the analytes in plasma stored at 6 degrees C was 8 hours for thrombin time, 24 hours for prothrombin time and activated partial thromboplastin time and 7 days for fibrinogen and antithrombin III. Factors V and VIII showed a decrease of 13 % and 20 % respectively after 8 hours. When the plasma of these patients was stored at room temperature, factor V was stable for 8 hours, and prothrombin time for 24 hours, whereas fibrinogen and antithrombin III remained unchanged for 7 days. Activated partial thromboplastin time showed an increase of 13 %, thrombin time a fall of 16 %, and factor VIII a decrease of 18 % after 8 hours.

Blood Coagulation

Specific pattern of circulating endothelial adhesion molecules in HIV-associated Kaposi's sarcoma.

BACKGROUND: Circulating endothelial adhesion molecules have been found to be increased in states of immune activation, but little is known about their significance in the assessment of endothelial neoplasms. One of the most common tumors supposed to be derived from endothelial origin is HIV-associated Kaposi's sarcoma (KS). METHODS: Plasma concentrations of sCD54 (= intercellular adhesion molecule-1), sCD106 (= vascular cell adhesion molecule-1), and sCD62E (= E-selectin) were quantified by sandwich ELISA in 54 AIDS patients who were either free of active opportunistic disorders (n = 15, AIDS controls), or suffering from acute infections (n = 16), or exhibiting KS (n = 23), and in 18 age- and sex-matched healthy HIV-negative controls. RESULTS: Both sCD54 and sCD106 plasma levels were consistently increased in all AIDS patients irrespective of concurrent opportunistic disorders (p < 0.005), while sCD62E levels were not altered in AIDS patients without KS (p > 0.05). In KS patients, sCD62E concentrations were decreased both compared to healthy (p = 0.0007) and to AIDS controls (p = 0.04), and stimulated sCD54 levels were less elevated than those of AIDS controls (p = 0.02). Plasma concentrations of all three adhesion molecules did not correlate to KS tumor stage. CONCLUSION: There appears to be a specific pattern of circulating endothelial adhesion molecules in AIDS patients with associated KS. Although the present findings do not support a role for their determination as tumor markers, they might be involved in KS tumor pathogenesis.

AIDS-Related Opportunistic Infections

Activation of the fibrinolytic system in patients with coronary artery disease and hyperfibrinogenemia.

Elevated fibrinogen levels as well as an impaired activity of the fibrinolytic system are regarded as important cardiovascular risk factors. To elucidate a potential interrelation between fibrinogen as an indicator of a hypercoagulable state and the endogenous fibrinolytic function hemostatic and rheological as well as lipid parameters were determined in 224 consecutive patients, who underwent elective coronary angiography. In the selected study population of 81 men and 19 women with fibrinogen concentration either > or = 3.5 g/l (n = 70) or < or = 2.5 g/l (n = 30) hyperfibrinogenemia was found to be significantly associated with increased concentrations of plasmin-alpha 2-antiplasmin complex [PAP [median (25.-75. percentile)], 534 (361-680) micrograms/l vs. 289 (243-440) micrograms/l; p < 0.001] and tissue plasminogen activator (t-PA) antigen [9 (6-11) micrograms/l vs 8 (5-9) micrograms/l; p < 0.05] while this association was lost in the subgroup of patients with angiographically normal coronary arteries (n = 26). In addition to these findings fibrinogen was significantly correlated with PAP (r = 0.40, p < 0.001; n = 224) and t-PA antigen (r = 0.2, p < 0.01; n = 224) after adjustment for age, diabetes mellitus, lipid parameters and leucocyte counts. It can be argued that elevated fibrinogen levels in patients with coronary artery disease are concomitant with an activation of the fibrinolytic system.

Blood Viscosity

[Endothelin and big endothelin in coronary heart disease and acute coronary syndromes].

Endothelin (ET), the most potent endogenous vasoconstrictor with mitogenic potency, is generated from its precursor big-endothelin (BET) in a proteolytic process and discussed as a pathogenetic factor in coronary artery disease and in the acute coronary syndromes. Several studies documented elevated plasma endothelin concentrations in acute myocardial infarction, but conflicting results were reported in patients with stable and unstable angina. Only few studies determined big endothelin, although it half-life and plasma concentrations are higher in comparison to endothelin. ET and BET levels (Radioimmunoassay, Biomedica GmbH, Vienna) were determined in patients with stable angina (SAP, n = 20), unstable angina (IAP, n = 12), acute myocardial infarction (AMI, n = 12) and healthy subjects (NP, n = 11). The concentrations of ET and BET (median (minimum-maximum) in fmol/ml) of the patients with stable angina (SAP: ET 0.7 (0.3-1.1); BET 1.7 (0.7-2.9)), unstable angina (IAP: ET 1.0(0.5-1.7); BET 2.5 (1.3-4.1)) and acute myocardial infarction (AMI: ET 1.2 (0.6-2.3); BET 3.6 (3.2-5.3)) showed a significant difference compared to controls (NP: ET 0.5 (0.4-0.7); BET 1.4 (1.1-1.7)) (SAP vs. NP: ET p < 0.01; BET p < 0.05; IAP and AMI vs. NP: ET and BET p < 0.001). Also, the concentrations of the peptides differed significantly dependent on the clinical severity of coronary artery disease (AMI vs. SAP: ET and BET p < 0.001; AMI vs. IAP: BET p < 0.05; IAP vs. SAP: ET p < 0.05; BET p < 0.01). Twelve of 15 patients with big endothelin concentrations over 3 fmol/ml suffered acute myocardial infarction. Seven of 12 patients with AMI showed elevated ET and BET concentrations before the increase of creatinecinase. There was no correlation between number of risk factors per patient, cholesterin and subfractions, severity of CAD classified in one-two-three-vessel disease or coronary score according to modified criteria of the American Heart Association (AHA). We conclude that in patients with coronary artery disease endothelin and big endothelin levels are elevated and related to the clinical and not to the morphological severity of coronary artery disease. Big endothelin is the more sensitive parameter in comparison to endothelin and indicates a severe course of myocardial ischemia in patients with unstable angina. The development of assays with the possibility of a quick determination of the peptides may be valuable for risk stratification of acute coronary events.

Adult

Monitoring of bone resorption after renal transplantation by measuring the urinary excretion of pyridinium cross-links.

The urinary excretion of pyridinium cross-links was measured in 70 second morning urine samples from 49 patients following renal transplantation. One and three months after renal transplantation, the urinary excretion of pyridinium cross-links was higher (p < 0.05) than at one week after transplantation. At all times after transplantation, the values for the excretion of pyridinium cross-links were correlated with the bone alkaline phosphatase concentrations (p < 0.001). However, there was no correlation between parathyrin concentrations and the values for the excretion of pyridinium cross-links (p > 0.05). This rise in the excretion of pyridinium cross-links is probably due to an increase of bone resorption caused by cyclosporin A and/or glucocorticoids. In the case of 17 urines with excretion values of pyridinium cross-links above the upper reference limit (pyridinoline equivalents, 93 mumol/mol creatinine), only 2 (12%) of the corresponding sera showed increased bone alkaline phosphatase values. In patients following renal transplantation simultaneous assessment of bone formation and bone resorption (determined from bone alkaline phosphatase serum concentrations and the excretion of pyridinium cross-links) may therefore enhance the diagnostic sensitivity for detecting effects on bone metabolism.

Adult

Storage of serum or whole blood samples? Effects of time and temperature on 22 serum analytes.

Information on the stability of serum analytes during storage of serum or whole blood samples is often incomplete and sometimes contradictory. Using a widely available analyser (Hitachi 737/Boehringer), we therefore determined the effects of storage time and temperature on the measured concentrations of the following serum analytes: sodium, potassium, calcium, chloride, inorganic phosphate, magnesium, creatinine, urea, uric acid, bilirubin, cholesterol, HDL- and LDL-cholesterol, triacylglycerols, creatine kinase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, alkaline phosphatase, alpha-amylase, lactate dehydrogenase and cholinesterase. When separated serum was stored at + 9 degrees C for seven days, the mean changes in inorganic phosphate and lactate dehydrogenase exceeded significantly (p < 0.05 or 0.001, respectively) the maximum allowable inaccuracy according to the Guidelines of the German Federal Medical Council; all other quantities were sufficiently stable. In serum at room temperature, inorganic phosphate, uric acid, HDL-cholesterol and triacylglycerols increased continuously, whereas bilirubin, LDL-cholesterol, creatine kinase and aspartate aminotransferase decreased more than the guidelines permit during the storage period (p < 0.05 for aspartate aminotransferase, p < 0.001 for the other analytes mentioned). In whole blood stored for 7 days at + 9 degrees C, only the following serum analytes satisfied the stability requirements of the guidelines: calcium, urea, cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, creatine kinase, gamma-glutamyltransferase and cholinesterase. When stored at room temperature, only sodium, uric acid, bilirubin, cholesterol, triacylglycerols, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, alpha-amylase and cholinesterase were still stable after 3 days. The data collected show that all quantities examined are sufficiently stable for four days in separated serum stored at + 9 degrees C.

Blood Chemical Analysis

Monitoring of osteoblast activity with an immunoradiometric assay for determination of bone alkaline phosphatase mass concentration in patients receiving renal transplants.

We examined the diagnostic validity of an immunoradiometric assay for determination of mass concentration of bone alkaline phosphatase (EC 3.1.3.1) in 134 sera from 35 patients receiving renal transplants. Comparison between bone alkaline phosphatase concentration and total alkaline phosphatase activity yielded a strong correlation (r = +0.860; P < 0.001). Nine (17%) of 54 sera which were characterized by a total alkaline phosphatase activity between 100 units/l and the upper reference limit (178 units/l (males) and 160 units/l (females), respectively) showed an increased bone alkaline phosphatase concentration (> 21.3 micrograms/l (males) and > 15.0 micrograms/l (females), respectively). There was also a correlation between bone alkaline phosphatase values and parathyroid hormone levels both before (r = +0.640 (n = 23), P < 0.001) and after renal transplantation (r = +0.528 (n = 111), P < 0.0001). A follow-up of 15 patients after renal transplantation revealed that the median of bone alkaline phosphatase values increased from 5.5 micrograms/l before transplantation to 14.9 micrograms/l 3 months after transplantation (P < 0.0001). Nevertheless no correlation could be observed between parathyroid hormone concentrations and bone alkaline phosphatase values at any time following renal transplantation in these 15 patients (P > 0.1). Rise of bone alkaline phosphatase concentration following renal transplantation is most probably due to an activating effect of cyclosporin A upon osteoblasts.

Adult

Efficacy of transferrin determination in human sera in the diagnosis of iron deficiency.

Apparently healthy persons (n = 425) as well as 264 patients characterized by an iron concentration in serum < 7.2 mumol/l were examined. A latent iron deficiency was defined as a concentration of ferritin < 20 micrograms/l (males) and < 15 micrograms/l (females), without anaemia; manifest iron deficiency defined by an additional presence of hypochromic microcytic anaemia. Fifty-nine of 425 (= 14%) apparently healthy persons showed a latent iron deficiency. In the remaining 366 we established the following reference intervals for the concentration of transferrin in serum [mumol/l]: 25.2-45.3 (males), 29.1-54.5 (females, < or = 25 years of age) and 25.3-48.6 (females, > 25 years of age). Eight of 59 (= 14%) apparently healthy persons with latent iron deficiency had a transferrin concentration above the reference interval. Sixty-one of 264 (= 23%) patients with an iron concentration < 7.2 mumol/l showed a ferritin concentration < 20 micrograms/l (males) and < 15 micrograms/l (females). Thirty-eight of these 61 patients (= 62%) had a manifest iron deficiency. In 18 of these 38 patients (= 47%) the transferrin concentration was increased. For our 264 patients we determined the diagnostic validity of an increased transferrin concentration for diagnosis of iron deficiency, assuming an iron deficiency if the concentration of ferritin remained below the discrimination values mentioned above: The diagnostic sensitivity was 36%, the diagnostic specificity 97%, the predictive value of the positive test result 79% and the predictive value of the negative test result 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Optimisation of a new continuous UV assay for the determination of blood coagulation factor XIII activity in human plasma.

The new photometric assay described by Fickenscher et al. (Thromb. Haemostas. 65 (1991) 535-540) for the determination of factor XIII facilitates the diagnosis of factor XIII deficiency. In spite of easy handling, this test should be used critically. Patients with hyperfibrinogenaemia showed factor XIII activities of less than 20%, whereas with an optimized assay we found normal factor XIII values. Also, the use of a fixed period of incubation for the analysis is questionable, because the period of constant reaction rate occurs earlier and is shorter with high factor XIII activities and later and longer with low factor XIII activities. A linear relation between factor XIII activity and signal only exists up to 80% of activity. In some plasma samples from patients with hyperfibrinogenaemia the factor XIII determination actually shows decreased values for factor XIII. During the reaction, a fibrin clot is formed. The resulting turbidity simulates an increase in absorbance so that NADH consumption is apparently decreased. In six patients with hyperfibrinogenaemia (8.1-9.4 g/l), a factor XIII activity of 26 U/l or less was determined. Using 50 microliters instead of 100 microliters sample volume, 50% (3/6) of the patients showed a normal factor XIII activities (80-96 U/l), whereas 50% (3/6) values of 6-15 U/l were found. In our modified assay we measured normal factor XIII activities (72-151 U/l) in all 6 patients. The procedure is optimized by reducing the sample volume from 100 microliters to 50 microliters.(ABSTRACT TRUNCATED AT 250 WORDS)

Factor XIII

[Filtration of buffy coat-free erythrocyte suspensions in additive solution].

Buffy coat-free red cell concentrates in SAG-M (RCC) were produced by BAT system (leukocyte content 132 x 10(6)/RCC). They were stored for 4 weeks and filtered by Erypur Optima (E), Sepacell R 500 B (S) und PALL RC 50 TM (P). Leukocyte depletion was very effective (E: 0.56 x 10(6)/RCC; S: 0.36 x 10(6)/RCC; P: 0.55 x 10(6)/RCC) but hemolysis was remarkable (E: 301 +/- 195; S: 127 +/- 123; P: 368 +/- 256 mg/RCC). Therefore preparation of two RCC per filter was only acceptable with S. In S and P loss of red cells was tolerable (E: 90.5; S. 41.8; P: 38.2). In contrast, E should be rinsed with sodium chloride at the end of the preparation. In E and S filtration times were short without additional pressure (E: 6.6 min; S: 4.7 min; P: 20.3 min). We conclude from our results that the use of buffy coat-free red cell concentrates in additive solution considerably reduces the problems of filtration, e.g. storage interval, leukocyte reduction, hemolysis, filtration flow. Despite this, bedside filtration is not recommended because quality assurance is necessary.

Blood Component Transfusion

[Production of rejuvenated and stable, leukocyte depleted erythrocyte concentrates using the heated centrifugation method].

We report on an alternative to filtration for the preparation of leukocyte-poor red cell concentrates (LP-RCC). It is based on the method of Schneider. Using RCC with buffy coat it is comparably effective in leukocyte reduction [98.3 +/- 1.0%, (3.7 +/- 2.6) x 10(6) leukocytes] and more effective in platelet reduction (96.9 +/- 2.5%). Addition of PAGGS-M before heating (30 min, 37 degrees C) as well as after preparation significantly reduces hemolysis (free hemoglobin, LDH, HBDH) and improves the quality of the LP-RCC (ATP, 2,3-DPG) during storage for 24 h after preparation. LP-RCCs prepared with PAGGS-M after 6-day storage show still better quality than before preparation and about the same quality as LP-RCCs 24 h after conventional preparation with saline solution. In conclusion, by use of PAGGS-M and sterile docking LP-RCCs of adequate quality for 6-day storage can be prepared, improving the supply of the patients concerned.

Adenine

Pediatrics.

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Child

Nocturnal asthma: slow-release terbutaline versus slow-release theophylline therapy.

In a double-blind cross-over study, the effects of slow release (S-R) terbutaline tablets (b.i.d. 0.25 mg/kg per day) and S-R theophylline (5.31 mg/kg morning and 10.62 mg/kg evening) were compared in eleven patients with nocturnal asthma. On day seven of each treatment period, drug serum concentrations and peak expiratory flow (PEF) were measured every 2h over a 24-h period. During daytime, terbutaline concentrations ranged from 1.6-14.1 (median 4.5) microgram/l and during the night from 2.1-18.7 (median 4.9) micron/l. Theophylline concentrations ranged from 3.9-24.3 (median 11.5) mg/l during the day and from 3.3-20.9 (median 10.4) mg/l at night. Nocturnal wheezing occurred during theophylline treatment in four patients 7 times and during terbutaline treatment in six patients 22 times. Daytime PEF values were 472 +/- 161 l/min during theophylline therapy versus 445 +/- 169 l/min during terbutaline therapy (p less than 0.05). In the night and early morning there was no significant difference between PEF values with the two treatment forms. During theophylline treatment, fewer inhalations of beta 2-sympathomimetics were used, and there were fewer side effects. One patient experienced severe asthmatic attacks during the terbutaline treatment period. The patients preferred theophylline for the treatment of nocturnal asthma.

Adult