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Biomedical subjects

J Conard

Publications and source records attributed to J Conard.

At least 19 recordsLinked to original sources
PubMed1992

Multicentric evaluation of a new assay for prothrombin fragment F1+2 determination.

A multicenter study of a recently developed ELISA for the determination of prothrombin fragment F1+2 was performed in order to evaluate analytical and clinical aspects. Mean intra-assay and inter-assay reproducibility were found to be 11.0 and 12.6%, respectively. The measuring range covered by the calibration curve reaches from 0.04 to 10.0 nM/l F1+2. Testing 133 healthy subjects a reference range of 0.37 to 1.11 nM/l F1+2 (2.5-97.5 percentile) with a median of 0.66 nM/l F1+2 was calculated. Minor difficulties with blood sampling (venous occlusion for 2 min) did not affect F1+2 plasma concentrations. Significantly increased F1+2 levels were measured in patients with leukemia (p < 0.0001), severe liver disease (p < 0.005) and after myocardial infarction (p < 0.01). Elevated F1+2 concentration before the beginning of heparin therapy (1.25 nM/l) decreased to 0.77 nM/l (p < 0.0001) after 1 day of therapy. For patients in the stable phase of oral anticoagulant therapy decreasing F1+2 concentrations were measured with increasing INR. F1+2 levels were already significantly reduced in patients with INR < 2.0 (0.56 nM/l; p = 0.0005). Thus F1+2 determination may be helpful in identifying activation processes as well as in monitoring anticoagulant therapy.

Administration, Oral↗
PubMed1992

Multicenter evaluation of three commercial methods for measuring protein S antigen.

This collaborative study was designed to assess the performance of commercial methods for protein S (PS) antigen measurement. Twenty-five different samples were distributed deep-frozen (24 plasmas) or lyophilized (one plasma) to five laboratories. They were analyzed blind in each laboratory by the method used locally and by three commercial methods which included two electroimmunoassays (EIA), Asseraplate-PS (Diagnostica Stago), Rellplate-S (American Diagnostica) and an ELISA system, Asserachrom-PS (Diagnostica Stago). 1. Reproducibility. Average between-laboratory coefficients of variation were 15.4%, 17.6% and 25.3% for Asserachrom-PS, Asseraplate-PS and Rellplate-S. 2. Specificity. Results of all methods showed that PS is underestimated when C4b binding protein is high. This influence was particularly evident for the ELISA Asserachrom-PS and disappeared when the antibody-antigen incubation period was prolonged to overnight. 3. Sensitivity. In all laboratories ELISA detected even the lowest PS concentration (4 U/dl), whereas the two EIAs were less sensitive (lower detection limit 14 U/dl). All methods and laboratories correctly diagnosed a plasma sample from a PS congenitally deficient patient. Conclusions. This study shows that better standardization of PS immunoassays is necessary to improve accuracy and reduce interlaboratory variability before a candidate plasma standard can be successfully calibrated in an international collaborative study.

Anticoagulants↗
PubMed1992

Pleiotropic effects of antithrombin strand 1C substitution mutations.

Six different substitution mutations were identified in four different amino acid residues of antithrombin strand 1C and the polypeptide leading into strand 4B (F402S, F402C, F402L, A404T, N405K, and P407T), and are responsible for functional antithrombin deficiency in seven independently ascertained kindreds (Rosny, Torino, Maisons-Laffitte, Paris 3, La Rochelle, Budapest 5, and Oslo) affected by venous thromboembolic disease. In all seven families, variant antithrombins with heparin-binding abnormalities were detected by crossed immunoelectrophoresis, and in six of the kindreds there was a reduced antigen concentration of plasma antithrombin. Two of the variant antithrombins, Rosny and Torino, were purified by heparin-Sepharose and immunoaffinity chromatography, and shown to have greatly reduced heparin cofactor and progressive inhibitor activities in vitro. The defective interactions of these mutants with thrombin may result from proximity of s1C to the reactive site, while reduced circulating levels may be related to s1C proximity to highly conserved internal beta strands, which contain elements proposed to influence serpin turnover and intracellular degradation. In contrast, s1C is spatially distant to the positively charged surface which forms the heparin binding site of antithrombin; altered heparin binding properties of s1C variants may therefore reflect conformational linkage between the reactive site and heparin binding regions of the molecule. This work demonstrates that point mutations in and immediately adjacent to strand 1C have multiple, or pleiotropic, effects on this serpin, leading ultimately to failure of its regulatory function.

Adolescent↗
PubMed1992

[Coagulation and bronchopulmonary cancers: from clinical aspects to biology].

Activation of coagulation and of the fibrinolytic system has been identified in small cell and non-small cell cancers respectively. For the clinician this poses the diagnostic problem of a thrombosis, which is most often venous with or without pulmonary emboli, complicating the evolution of an already diagnosed cancer. The inverse is that these features may reveal an underlying neoplasm and amongst the most common of these would be bronchopulmonary cancer. Numerous laboratory studies have shown the existence of a state of hyper-coagulability, with disseminated intra-vascular coagulation, which is more or less compensated and is the more marked, the more advanced the cancer is. One should not fail to recognise that this state of hyper-coagulability may be aggravated by certain cytotoxic drugs. At the level of the tumour itself, there seems to be interactions between the cancer cells and the coagulation and fibrinolytic system: these interactions are very different according to the histological type as to whether they are small cell or non-small cell bronchopulmonary cancers.

Anticoagulants↗
PubMed1991

Lupus anticoagulant associated with primary malignant lymphoplasmacytic lymphoma of the spleen: a report of four patients.

Primary lymphoma of the spleen is characterized by predominant splenomegaly. Lymphoplasmacytic malignant lymphoma of the spleen, of low malignancy in the Kiel classification, low and intermediate grade in the National Cancer Institute Working Formulation (NCIWF), is rare. It is often associated with a monoclonal immunoglobulin M (IgM). Four patients presenting with primary splenic lymphoma of plasmacytic type associated with a high level of monoclonal IgM and a lupus anticoagulant (LA) are described. This association has not previously been reported. In contrast with the usual heterogeneity of LA, this LA is relatively homogeneous with an important prolongation of the prothrombin time (greater than 18 sec for a control of 12), more prolonged partial thromboplastin time (PTT) of the mixture patient + control plasma than PTT of the patient plasma. Despite the important coagulation abnormalities, none of these four patients has presented any hemorrhagic or thrombotic complications, even during major surgery such as splenectomy. The lupus-like anticoagulant effect ran parallel with the monoclonal IgM. Survival, after splenectomy and chemotherapy, appears to be favourable: three patients are alive with survivals of greater than or equal to 7 years. The follow-up is as yet too short for the last patient.

Adult↗
PubMed1991

Effects of nomegestrol acetate (5 mg/d) on hormonal, metabolic and hemostatic parameters in premenopausal women.

The effects of nomegestrol acetate on circulating hormone levels, metabolic and hemostatic parameters and blood pressure were studied in 36 premenopausal women. The progestogen was administered from day 7 to 25 of the cycle during six cycles at a dosage (5 mg/d) known to inhibit ovulation. Analysis were performed before and in the third and sixth cycles. Estradiol and progesterone levels decreased significantly (p less than 0.001) during treatment. Body weight, fasting blood glucose and insulin, total HDL and LDL cholesterol, apolipoprotein B, fibrinogen and plasminogen did not change significantly. Triglycerides in the third cycle (p less than 0.05) and apolipoprotein A1 levels (p less than 0.01) in both periods of sampling decreased significantly. There was a significant increase in antithrombin III (p less than 0.01). These results indicate that nomegestrol acetate has no deleterious effect on blood glucose and lipids. The decrease in apolipoprotein A1 and increase in antithrombin III may be related either to the decrease in estradiol levels induced by the treatment or to the effect of the progestogen itself.

Adolescent↗
PubMed1991

Anti Xa activity and prothrombinase inhibition in patients treated with two different doses of enoxaparin in gynecologic surgery.

A prospective open study was performed in a series of 547 patients undergoing gynecologic surgery. A dose of 20 mg of enoxaparin was administered to all patients 2 hours before surgery. Then patients at high risk of thrombosis (mostly oncologic surgery) received 40 mg of enoxaparin daily whereas those at moderate risk received 20 mg of enoxaparin daily. The principal aim of this prospective open study was to monitor amidolytic anti Xa activity and to study the inhibition of intrinsic prothrombinase using prothrombin consumption measurement as a simple and global test. A second aim was to investigate efficacy and tolerance of these regimens. Treatment tolerance was satisfactory with both regimens since the total incidence of bleeding was 1.8%. A single patient developed a clinically significant thrombosis during hospital stay. The results confirm and extend previous reports regarding a dose effect relationship between the dose of Enoxaparin and plasma Anti Xa activity 3 hours after s.c. injection. A significant relationship was found between Anti Xa activity and patients body weight. Interestingly a dose dependent inhibition of intrinsic prothrombinase was observed when using a one stage prothrombin consumption assay in whole blood. This test in whole blood can be considered as closer to physiological conditions than assays performed in citrated platelet rich or platelet poor plasma samples. The mechanism of intrinsic prothrombinase inhibition during prophylactic treatment with enoxaparin requires further investigation.

Adult↗
PubMed1990

[Biological monitoring of treatment with antivitamin K. Value of INR and definition of new therapeutic ranges. A study of 73 patients].

The prothrombin time test (PT) is the most common method used for monitoring oral anticoagulant therapy. As a consequence of the variability in responsiveness of different thromboplastins, PT results obtained from patients on oral anticoagulant therapy may not be interchangeable between laboratories and as consequence could produce potential problems for anticoagulant control. The conversion of PT in INR (International Normalized Ratio) has been introduced recently to standardise the PT used for anticoagulant control. 127 determinations of prothrombin time and INR with 2 different thromboplastin reagents (Thromboplastin C Dade and Owren reagent) have been performed in 73 patients. This study confirm the usefulness of the INR (INR discrepancy in 10% of the cases) despite the imperfections concerning the choice of the control plasma and the need of a precise measurement of the ISI, International Sensitivity index. In parallel, changes in therapeutic ranges for anticoagulant therapy occurred, based on results of the international literature: less intense anticoagulant treatment (INR 2-3) is effective against recurrent venous thromboembolism with reduced bleeding. Different therapeutic ranges must be recommended for oral anticoagulant therapy according to the indication of the treatment.

Administration, Oral↗
PubMed1989

A 32 kDa lipocortin from human mononuclear cells appears to be identical with the placental inhibitor of blood coagulation.

A 32 kDa protein isolated from human mononuclear cells is a member of the lipocortin family, a new group of Ca2+-dependent lipid-binding proteins thought to be involved in the regulation of phospholipase A2, in exocytosis and in membrane-cytoskeleton interactions. Purification of this protein was based on its ability to associate with membrane phospholipids in a Ca2+-dependent manner and its capacity to inhibit purified phospholipase A2 from pig pancreas. Using immunological detection, we show that it is present in various cells involved in the inflammatory and coagulation processes. We present extensive amino acid data that strongly suggest that this protein is identical with a recently described inhibitor of blood coagulation, with endonexin II and with lipocortin V. Sequence alignment with other known proteins show a significant degree of homology with lipocortins I and II, the substrates of the epidermal-growth-factor receptor tyrosine kinase and the oncogene pp60src tyrosine kinase respectively, and with protein II. The possible physiological role of this 32 kDa lipocortin is discussed.

Amino Acid Sequence↗
PubMed1989

Comparative metabolic study of percutaneous versus oral micronized 17 beta-oestradiol in replacement therapy.

The aim of this study was to compare the metabolic effects of two presentations of 17 beta-oestradiol (E2) which are of recognized effectiveness in the prevention of post-menopausal bone loss, one being administered via the oral and the other via the percutaneous route. During this prospective, randomized study, 32 patients were treated for 2 mth with either 2 mg/day of oral micronized E2 (n = 16) or 1.5-3 mg/day of percutaneous E2 (n = 16). Both regimens proved efficacious, since significant increases in oestrone (E1) and E2 concentrations ranging up to mid-follicular values were observed. In the percutaneous-treatment group we noted a significant decrease in triglycerides (TG), without any significant changes in high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). In the oral-treatment group, we saw no significant increase in HDL-C, although significant increases were observed in body weight, TG, plasma renin substrate (PRS) and sex-hormone-binding globulin (SHBG) as well as significant decreases in antithrombin III (AT III) activity and antigen. All of these metabolic variations led us to the conclusion that oral E2 at the dose established as effective in preventing post-menopausal osteoporosis may, even when micronized, alter certain metabolic and haemostatic parameters in a population characterized by increases in cardiovascular risk factors and morbidity. Oral oestrogen replacement therapy should therefore continue to be used only in carefully selected patients and be strictly followed up by systematic checks on a series of metabolic criteria.

Administration, Cutaneous↗
PubMed1989

[Intravenous thrombolysis with tissue plasminogen activator (rt-PA) at the prehospital phase of acute myocardial infarction. Apropos of 49 cases].

In acute myocardial infarction, the earlier intravenous thrombolysis is performed the more effective its action. Pre-hospital intravenous thrombolysis with 100 mg rt-PA was carried out in 49 patients within 3 hours of myocardial infarction. Male preponderance was conspicuous with 44 men (92%) and only 5 women (8%). Mean age was 50.2 +/- 8 years. The infarction was inferior in 48% of the cases. Out of the 49 thrombolyses performed by the mobile intensive care unit, 3 were discontinued on admission (2 diagnostic errors, 1 external heart massage). The time gained by pre-hospital thrombolysis was 52 +/- 25 minutes. There were few complications of thrombolysis: blood effusion at the site of puncture occurred in 4 cases (9%) and haematemesis in 1 case (2%). No cerebral or lethal haemorrhage was observed. Major complications of MI were seldom encountered at the pre-hospital phase: 1 patient died of extensive anterior necrosis with left ventricular dysfunction, and 2 had reversible ventricular fibrillation before treatment was initiated. There was no haemorrhagic complication. The earlier the patient was treated the lower the mortality and morbidity rates. Pre-hospital thrombolysis therefore seems to be feasible when performed by a mobile intensive care unit, and it represents an important gain of time.

Adult↗