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Biomedical subjects

F Duckert

Publications and source records attributed to F Duckert.

At least 19 recordsLinked to original sources

Anticardiolipin antibodies and coronary heart disease.

Arterial or venous thrombotic events have been described as complications in patients with positive anticardiolipin antibodies (aCL), affecting various organs including the heart. In order to see whether aCL could be, among others, a predisposing factor for coronary artery occlusions and whether it could serve as a prognostic marker for coronary heart disease, 232 patients enrolled in the European Concerted Action on Thrombosis Angina Pectoris Study were studied. aCL and various other haemostatic parameters were determined at time of admittance in order to see whether a relationship existed between haemostasis at baseline and extent or prognosis of the cardiovascular disease. A follow-up at 12 and 24 months after angiography included information about relapsing coronary or other thrombotic events, treatment and outcome of the disease. aCL were not found to be a marker of either progressive cardiovascular disease or recurrent thrombotic events. No correlation was found, either in aCL positive or in aCL negative patients, between high levels of haemostasis activation markers, such as beta-thromboglobulin, platelet factor 4 or fibrinopeptide A and recurrent cardiovascular disease.

Aged

What happens to drinking after therapeutic intervention?

Eighty-four men and 51 women who had been recruited to treatment through newspaper advertisements were matched pairwise and randomly assigned to either brief counselling or short-term group therapy. All participants were followed-up after 3, 9, 15 and 21 months by personal interviews and medical examinations. The average reduction in alcohol consumption was greatest to start with in the group attending group therapy, but this group experienced greater set-back during the following period. At 21 months there were no significant differences between the two groups as regards amount of alcohol consumed, GGT-levels, deaths or number of alcohol-related hospitalizations. The sample as a whole maintained a significant reduction in alcohol consumption throughout the follow-up period. At 21 months half of the sample had reduced their consumption with more than 50%, one-fourth had reduced 20-50%, one-tenth changed less than 20% and only 18% of the sample had increased their consumption with more than 20% compared with their baseline consumption. The reductions took place mainly by way of less frequent drinking, fewer episodes of heavy drinking and reduced consumption during weeks of moderate drinking. When heavy drinking episodes did occur, there were only minor changes in the amounts consumed.

Adult

Co-variation between biological markers and self-reported alcohol consumption. A two-year study of the relationship between changes in consumption and changes in the biological markers gamma-glutamyl transpeptidase (GGT) and average volume per erythrocyte (MCV) among problem drinkers.

Co-variations between self-reported alcohol consumption and the biological markers MCV (average volume per erythrocyte) and GGT (gamma-glutamyl transpeptidase) over a 2-year period were studied in a group of 84 men and 53 women recruited to out-patient treatment by advertisements in the press. Upon admission, the drinking pattern of the participants during the preceding year was registered in detail. The participants were also medically examined, and blood samples taken. All the participants were followed up by new personal interviews, medical examinations and new blood sampling after 3, 9, 25 and 21 months. For the group as a whole, alcohol consumption was significantly lower at the end of the observation period than at admission. GGT was also decreased, but not MCV. Both self-reported consumption and the values for the biological markers showed large inter-individual and intra-individual variations during the observation period. The biological markers seemed to co-vary to a limited degree with changes in reported consumption. Both GGT and MCV seemed to have a low sensitivity but a high specificity to changes in consumption. Both markers also seemed to be somewhat more useful in identifying decreases than increases in consumption. The markers GGT and MCV should be used with caution in connection with therapeutic counselling to individuals.

Adult

The impact of sequential quality assessment exercises on laboratory performance: the multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT).

As an adjunct to a European multicentre prospective study, five quality assessment (QA) exercises, spanning a period of 2.5 years, were undertaken. In these, fifteen laboratories from eight countries each performed ten haemostatic factor assays. The design of the QA exercises allowed the between-duplicate, between-day and between-laboratory coefficients of variation (CVs) to be calculated. The between-duplicate CV decreased by a factor of one quarter, and the between-day CV by a factor of one third, over the five exercises. The activated partial thromboplastin time (APTT) assay consistently showed the lowest CVs, while there was notable improvement in the between-day CVs for von Willebrand factor related antigen (vWF R:Ag) and factor VIII clotting activity (VIII:C). However, the between-laboratory CV, assessing extent of agreement between the different laboratories, did not apparently improve over the five exercises. Thus, while QA exercises may be very useful in improving the performance of haemostatic assays according to criteria which an individual laboratory can assess, improving agreement on haemostatic assay results between laboratories may be more difficult to achieve.

Angina Pectoris

[Disulfiram and calcium carbimide. Mode of action, adverse effects and clinical use].

The alcohol-sensitizing drugs disulfiram and calcium carbimide are often used in the treatment of alcohol problems with the hope of reducing alcohol consumption. These drugs inhibit the liver enzyme acetaldehyde dehydrogenase and, when taken prior to ethanol, produce an acetaldehyde-mediated aversive reaction. However, the drugs are unspecific, and several side effects may be related to their influence on other biochemical processes. These drugs are primarily pharmacological adjuncts and should be used in conjunction with behavioural and psychosocial therapies.

Alcoholism

Patterns of contact phase proteins indicating neuropathy in diabetic patients.

In 42 outpatients of the diabetology division, coagulation and fibrinolysis variables were determined in order to detect typical patterns of results with which it was possible to discriminate between three groups with different diabetic complications (17: no complication, 7: angiopathy alone, 18: neuropathy with or without other complications). There was a statistically significant discriminatory function involving C1-inhibitor concentration, high molecular weight kininogen coagulant activity and fibrinogen as the most decisive variables. The neuropathy group was appropriately separated from the others with an 81% correct reclassification. Heparin cofactor II, histidine-rich glycoprotein, alpha 2-macroglobulin, pre-kallikrein and factor XII had no discriminative power.

Adult

von Willebrand factor and factor VIII in renal transplant recipients under immunosuppression with cyclosporine and steroids. Sequential measurements over 4 months in 17 patients.

In 17 consecutive cadaver kidney transplant recipients treated with cyclosporine (CsA) and steroids, the median of antigenic and functional levels of von Willebrand factor (vWF) and factor VIII (FVIII) before transplantation were elevated (vWF:Ag: 206%, vWF:RCof: 202%; FVIII:Ag: 248%, FVIII:C: 224%; normal values 50-150%). Sequential measurements after transplantation and during CsA treatment revealed a transient significant increase of median values with highest amounts of vWF:Ag of 362% (2 p less than 0.0001), FVIII:Ag of 398% (2 p less than 0.001) and FVIII:C of 360% (2 p less than 0.0001) (Friedman test). vWF:RCof did not show statistically significant changes. After 4 months, levels of vWF and FVIII comparable to those obtained before transplantation were observed. In univariate statistical analysis no correlation was found between vWF of FVIII on the one hand and plasma creatinine levels, CsA dose or CsA whole blood through levels on the other hand. However, multivariate statistics revealed to some extent a positive influence of CsA blood levels on vWF:Ag levels. Patients with vascular rejection or chronic CsA nephrotoxicity showed significantly lower levels of vWF:Ag as compared with patients without endothelial cell damage in the kidney (2 p less than 0.05). However, the difference in vWF:Ag levels already existed before transplantation. In contrast to recent reports, plasma vWF levels were not indicative of vascular injury in kidney graft recipients nor was the marked elevation of vWF and FVIII associated with thromboembolic complications ascribed to CsA treatment.

Cadaver

Impaired fibrinolysis as an essential contribution to thrombosis in patients with lupus anticoagulant.

Lupus anticoagulants (LA) are IgG or IgM antibodies against phospholipids which in vivo represent an important thrombophilic factor despite their in vitro anticoagulant activity. We investigated the fibrinolytic system of 20 patients with connective tissue disease and positive LA, compared to a control group of 24 age- and disease-matched patients without LA. There was no statistically significant difference of alpha 2-antiplasmin, plasminogen, fibrinogen, t-PA activity, D-dimers and heparin cofactor II, between the two groups. Although t-PA was uniformly low in both groups, plasminogen activator inhibitor activity (PAI) was significantly higher in LA cases (p less than 0.001). Increased PAI levels represent an inhibitory factor of the fibrinolytic defense mechanism, which together with other functional deviations may contribute to the thrombophilic tendency of LA patients.

Autoantibodies

The measurement of haemostatic factors in 16 European laboratories: quality assessment for the Multicentre ECAT Angina Pectoris Study. Report from the European Concerted Action on Thrombosis and Disabilities (ECAT).

As part of a European multicentre prospective study involving the measurement of a number of haemostatic factors, a quality assessment (QA) scheme was organized. This paper describes the preparation, design and results of the first QA exercise, involving 16 European laboratories and 10 haemostatic assays. The design allowed the investigation, for each assay, of the variability between duplicates and the variability between days within each centre, and of the agreement between centres. A graphical presentation of each centre's performance in comparison to that of others was adopted, which preserved the confidentiality of each centre's results. The factor VIII clotting activity assay (VIII:C) and the rocket immuno-electrophoresis assays of von Willebrand factor related antigen (vWF R:Ag), antithrombin III, protein C and histidine-rich glycoprotein showed the highest between-duplicate and between-day coefficients of variation (CVs), whereas the clotting assays of activated partial thromboplastin time and fibrinogen had the lowest CVs. CVs for the enzymatic assays using synthetic substrates of antithrombin III, plasminogen and alpha-2-antiplasmin were between these extremes. The between-centre CVs were high for both the VIII:C and vWF R:Ag assays. The QA exercise showed that, in multicentre studies involving the measurement of haemostatic factors, it is feasible to undertake analysis locally at each centre.

Angina Pectoris

Ethanol elimination-rates determined by breath analysis as a marker of recent excessive ethanol consumption.

The rate of ethanol elimination was studied in two groups of men by means of an Alcotest 7010 breath analyser. The experimental group consisted of 15 skid-row alcoholics undergoing detoxification. Their median daily ethanol consumption was 211 (range 26-476) g pure ethanol during the last year. The control group was made up of 12 age-matched healthy social drinkers consuming 9 (range 4-23) g day-1 pure ethanol during the last year. The median ethanol elimination-rate in the elimination phase was 0.25 (range 0.13-0.31) g 1-1 h-1 during the detoxification period in the experimental group. This value was approximately 70% higher than in the control group (0.14(0.12-0.17) g 1-1 h-1). Some correlation was found between reported ethanol intake, and the calculated ethanol elimination-rate, as well as gamma glutamyl transferase (GGT), alanine amino transferase (ALAT), aspartate amino transferase (ASAT), glutamate dehydrogenase (GLDH), mean corpuscular volume (MCV) and HDL-cholesterol. Of these measures, ethanol elimination-rate showed highest sensitivity and efficiency for detection of ethanol consumption above the limit of 50 g per day.

Adult

Factor XII, plasma prekallikrein, alpha 2-macroglobulin and C1-inhibitor levels in renal allograft recipients during immunosuppression with cyclosporin A--sequential measurements over four months in 17 patients.

Factor XII clotting activity (F XII), plasma prekallikrein amidolytic activity (PK), alpha 2-Macroglobulin (alpha 2-M) and C1-Inhibitor (C1-Inh) antigens have been measured in 17 patients immediately before and sequentially for up to four months after kidney transplantation. Before transplantation mean F XII and PK levels were normal (99 +/- 27% and 102 +/- 21%, respectively, mean +/- S.D.) and alpha 2-M and C1-Inh levels were slightly elevated (115 +/- 55% and 129 +/- 32%, respectively, mean +/- S.D.). In the first two weeks after transplantation a significant decrease of F XII to 65 +/- 27%, of PK to 67 +/- 20% and of alpha 2-M to 88 +/- 42%, and a rise of C1-Inh to 201 +/- 44% (mean +/- S.D.) were observed (2 p less than 0.005). F XII levels four month after operation remained significantly (2 p less than 0.05) lower than preoperatively. PK and alpha 2-M values, however, were significantly higher (2 p less than 0.05) at four months as compared to the pretransplant period. Mean F XII levels in the 17 patients at various time points after transplantation correlated positively with PK, alpha 2-M and serum albumin and negatively with CyA level and dose and serum bilirubin. PK and alpha 2-M correlated positively with each other and albumin and negatively with creatinine, bilirubin and CyA (2 p less than 0.01). Whether CyA has a direct influence on production or consumption of F XII, PK, alpha 2-M and C1-Inh, or whether the changes merely reflect altered protein metabolism awaits further study.

Adult

Association of hereditary heparin co-factor II deficiency with thrombosis.

A family was investigated for heparin co-factor II deficiency. Three of the five members examined had had thrombosis and their levels of heparin co-factor II were reduced to 50%. All five members had antithrombin III levels within the normal range. Analysis on crossed immunoelectrophoresis showed no qualitative abnormality of patient heparin co-factor II antigen. Since heparin co-factor II activity and concentration were reduced to the same extent, the deficiency was due to reduced protein synthesis.

Adult

[Fibrinolysis therapy in massive lung embolism. Experiences in 10 patients 1982-1984].

Between October 1982 and July 1984 systemic thrombolysis was carried out in 10 patients (5 males and 5 females aged 19 to 66 years) with massive pulmonary embolism (PE). Mean thrombolytic treatment duration was 77 hours. The main fibrinolytic agent used (9 cases) was streptokinase. Sequential treatment with streptokinase and urokinase was given to 2 patients and urokinase alone to one. 5 patients received porcine plasmin additionally, and one patient BRL 26921 (streptokinase-plasminogen complex) and human plasminogen. Pulmonary arterial pressures were recorded serially. Pulmonary angiograms were obtained before, occasionally during and after thrombolysis. Pulmonary arterial pressures (systolic: p less than 0.01, diastolic: p less than 0.05, mean: p less than 0.01, paired t-test, two tailed) and pulmonary angiograms (p less than 0.001, paired t-test, two tailed) all showed significant improvement. Thrombolytic treatment had to be discontinued in two patients due to side effects. Patients with the most recent PE showed the best response. Patients with recurrent PE and preexisting pulmonary hypertension showed no improvement. In PE without deep vein thrombosis (DVT), treatment duration of up to three days seems to be appropriate. In PE with concomitant DVT the treatment should be prolonged to achieve complete lysis of thrombi.

Adult

Cold promoted activation and factor XII, prekallikrein and C1-inhibitor.

During incubation of plasma in the cold an amidolytic activity due to the kallikrein-alpha 2-macroglobulin complex appears in the plasma of about 40% of the women under hormonal contraception. The factor XII and prekallikrein activity are significantly increased 151.9% and 112.4% respectively in the cold promoted activation positive plasmas (CPA pos) whereas the activity of C1-inhibitor is decreased, 76%. The quotient of the product of the C1-inhibitor and alpha 2-macroglobulin values divided by the product of the FXII and prekallikrein values is significantly lower in the CPA pos plasma 0.49 than in CPA neg plasma 0.96 (p less than 0.05). These results alone do not explain the cold promoted activation, since a patient with a C1-inhibitor as low as 9% showed no increase of the amidolytic activity after a 24 hr incubation at 4 degrees C. However, the addition of purified C1-inhibitor to a CPA pos. plasma inhibits the cold activation. Heparin at a concentration of 0.5 IU/ml delays the appearance of the amidolytic activity.

Adolescent

[Control of oral anticoagulation: comparison between Quick and colorimetric factor X determination in 107 patients].

Since monitoring of oral anticoagulation (OA) by prothrombin time (PT) is a source of standardization difficulties, the authors have tested another approach. 107 patients under long term OA were monitored by both PT and a colorimetric factor X assay (in vitro activation of factor X with RVV and assessment of amidolytic activity towards S-2222). The PT values were between 10 and 34% (therapeutic range 15--25%), and factor X levels were between 10 and 44% (therapeutic range 16--24%). The correlation between the two methods was highly significant (r = 0.65, p less than 0.001). In 68% of the patients the two tests gave the same information (55 subjects were adequately, 16 insufficiently and 2 over-anticoagulated). For a slightly broader therapeutic range (PT 15--30%, corresponding to 16--28% factor X) concordant information was obtained in 82% of the patients. During stable OA, PT and factor X assay gave very similar information. An advantage of the latter method is the possibility of automation, while a disadvantage is its insensitivity to factor VII.

Administration, Oral

[Dissociation of human factor VIII and recombination of the fragments VIII-C and VIII-AG].

Human factor VIII has been dissociated into fragment VIII-C and fragment VIII-AG in the presence of calcium chloride (0.25 M). After removing the calcium, recombination of the molecule is obtained. Fragment VIII-C can be activated by thrombin in a similar manner to the coagulant activity of whole factor VIII. This activation is calcium-dependent. In rabbits immunized against purified F VIII, VIII-C and VIII-AG specific antisera against these three entities were obtained.

Blood Coagulation Tests

[Basle family study. Organization and 1st results].

The organisation of the Basle Family Study and preliminary results outlining the data analysis are presented. The study investigates in 500 families the familial influence on risk factors for cardiovascular diseases. In addition the distribution of hemostatic variables is studied. Analysis of the data according to age, sex and intrafamilial relations in 211 families demonstrate the influence of the mother on the development of the life style of the children.

Adolescent