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Biomedical subjects

A S Gallus

Publications and source records attributed to A S Gallus.

At least 55 records · Page 3Linked to original sources
PubMed1987

The relative contributions of antithrombin III during heparin treatment, and of clinically recognisable risk factors, to early recurrence of venous thromboembolism.

The influence of antithrombin III (ATIII) level and ATIII activity, measured during intravenous heparin treatment for venous thromboembolism (VTE), on 'heparin requirement' (the heparin dose required to prolong the activated partial thromboplastin time (APTT) into its designated therapeutic range), and on the likelihood of recurrent VTE during the first month of anticoagulant therapy, were examined in a prospective study of 232 patients with VTE treated according to a standard protocol. 15 patients with recurrent VTE (6.5%) had a lower mean APTT during heparin treatment than patients without recurrence; a finding due partly to their heparin requirement. However, there was no measurable relationship between ATIII level or ATIII activity and either heparin requirement or recurrence of VTE. By contrast, both the presence of disseminated malignancy and the development of heparin induced thrombocytopenia were powerful, clinically recognisable, risk factors for recurrence during or soon after heparin therapy.

Adolescent↗
PubMed1987

Antithrombin III deficiency: clinical relevance and replacement therapy.

Inherited antithrombin III (ATIII) deficiency causes a life-long tendency to venous thromboembolism, which is often recurrent and may be life-threatening. In contrast, the clinical importance of acquired ATIII deficiency, whether spontaneous or associated with estrogen-containing oral contraceptive treatment, remains uncertain. Moderately reduced ATIII activity before or immediately after surgery is neither sensitive nor specific for a high risk of postoperative venous thromboembolism (VTE), while moderately reduced ATIII activity during heparin treatment for VTE fails to indicate an unusually large heparin requirement or to predict recurrence. In the absence of good clinical trials, the value of ATIII replacement therapy also remains obscure; its use in congenital deficiency is largely based on anecdote, and while it may cause more rapid correction of the hemostatic defect in patients with disseminated intravascular coagulation (DIC), any improvement in morbidity or mortality resulting from ATIII replacement remains to be demonstrated.

Antithrombin III↗
PubMed1986

The use of antithrombotic drugs in artery disease.

Evaluating the use of antithrombotic drugs in artery disease has been a long and difficult process, which is far from complete. The aims of treatment have ranged from the primary prevention of myocardial infarction or stroke, through the restoration of blood flow to ischaemic organs in order to salvage threatened tissue, to the prevention of recurrent vascular occlusion. Drugs studied in depth by clinical trial include the oral anticoagulants, antiplatelet drugs (especially aspirin), and thrombolytic agents. Their results are considered under the headings of coronary artery disease, cerebral ischaemia, and peripheral vascular disease. Aspirin, with or without dipyridamole, prevents progression of unstable angina to myocardial infarction or death, probably reduces long-term mortality after myocardial infarction, and prevents aortocoronary bypass graft occlusion. It decreases the risks of stroke or death in patients with transient cerebral ischaemia, diminishes cardiovascular morbidity after a thrombotic stroke, and may improve the outcome after some kinds of surgery for peripheral vascular disease. The benefits of oral anticoagulant treatment to prevent artery occlusion remain poorly defined. Oral anticoagulants prevent systemic embolism in many groups of high-risk patients, and probably reduce the risk of recurrence after embolism has occurred. Whether their long-term use to prevent reinfarction in patients with a previous myocardial infarct can be justified remains uncertain. They are of little or no proven value in patients with transient cerebral ischaemia or thrombotic stroke. On the other hand, there is increasing support for early thrombolytic treatment after myocardial infarction, especially since two multicentre trials have now shown reduced mortality in patients treated with intracoronary streptokinase within 4-6 hours of infarction and a further large multicentre study also demonstrated reduced mortality in patients treated with early intravenous streptokinase. In addition, the local infusion of streptokinase leads to recanalization in a high proportion of patients with a recent peripheral artery occlusion who are poor candidates for surgery.

Angina, Unstable↗
PubMed1985

Aspirin and other platelet-aggregation inhibiting drugs.

The biochemistry of platelets is surprisingly complex, and offers the opportunity for numerous platelet-aggregation inhibiting ("antiplatelet") drugs to interfere with different aspects of their metabolism and function. Thus, aspirin inhibits platelet aggregation by irreversibly inactivating cyclo-oxygenase, a key enzyme in platelet prostaglandin metabolism, while the other nonsteroidal anti-inflammatory drugs and sulphinpyrazone cause reversible and dose-dependent inhibition of the same enzyme. Dipyridamole can inhibit both platelet adhesion and aggregation by raising the platelet cyclic AMP level through phosphodiesterase inhibition. The use of aspirin, sulphinpyrazone, and dipyridamole as antithrombotic agents has now been extensively evaluated. In general, treatment with these drugs has been more likely to prevent arterial than venous thromboembolism, and aspirin or the combination of aspirin and dipyridamole has been more effective in this respect than has sulphinpyrazone. Recent evidence strongly suggests that aspirin reduces the risk of non-fatal myocardial infarction in patients with unstable angina, and that the administration of aspirin in combination with dipyridamole significantly improves graft patency after aortocoronary bypass. Aspirin also appears to reduce the likelihood of stroke or death in men with transient cerebral ischaemic attacks.

Aspirin↗
PubMed1985

Intermittent claudication: a double-blind crossover trial of pentoxifylline.

The influence of the xanthine derivative pentoxifylline ('Trental' or BL191; Hoechst-Roussel) on exercise tolerance was measured in 38 subjects with stable, severe to moderately severe, intermittent claudication who completed a randomised, double-blind, placebo controlled, cross-over clinical trial. Patients received placebo tablets or 400 mg slow-release pentoxifylline tablets ('Trental 400') twice a day for one week, followed by three times daily for seven weeks, and then crossed over to receive the alternate preparation for another eight weeks. Claudication distance and walking distance were measured on a treadmill before starting treatment and again at four-week intervals during the trial. At the same times, red blood cell filterability, plasma fibrinogen concentration and blood viscosity, resting and post-ischemic calf muscle blood flow, and the resting and post-exercise ankle/brachial systolic pressure ratio were also measured. In this study, the observed effects of pentoxifylline treatment were no greater than those of placebo, even though serum levels of pentoxifylline and its hydroxy-metabolite were within the anticipated range. This was shown by a 'therapeutic effect ratio' of 0.98 for treadmill claudication distance and 0.96 for treadmill walking distance after within-patient analysis at the end of the cross-over (where a ratio of 1.0 means the test drug and placebo effects are identical). These ratios have 95% confidence limits of 0.72-1.34 and 0.74-1.25, respectively.

Aged↗
PubMed1984

Oral contraceptives and surgery: reduced antithrombin and antifactor Xa levels without postoperative venous thrombosis in low-risk patients.

The effect of preoperative treatment with an estrogen containing oral contraceptive on the incidence of postoperative thrombosis (detected with 125I-fibrinogen leg scanning) was examined in 221 patients aged 18-49 years who had elective or emergency general intra-abdominal or gynecologic surgery, 99 of whom were taking an oral contraceptive before their operation. Eighty-five percent of the contraceptive treated patients had taken their preparation until 1-7 days before surgery and the rest until within a month of surgery; 81% were taking preparations containing 30 or 50 micrograms estrogen. Postoperative thrombosis developed in 1 of the 122 patients who were not taking a contraceptive and in none of the 99 contraceptive treated patients. As the 95% confidence limits for the 0% thrombosis rate observed in the contraceptive treated patients are 0-3.7%, the added risk of postoperative thrombosis attributable to oral contraceptive treatment before surgery is very small in young women who are otherwise at low risk of thrombosis. Plasma antithrombin level (by immunoassay), antithrombin activity (by chromogenic substrate assay), and antifactor Xa activity (by clotting assay), were measured before surgery in 81 patients, 42 of whom had been taking an oral contraceptive. Contraceptive treatment significantly reduced all 3 assay results. Its most marked effect was on antifactor Xa activity, which was reduced by contraceptive treatment from 103 +/- 24% (range 68 - 172%) to 81 +/- 27% (range 24 - 155%; with less than 80% activity in 54%, and less than 50% activity in 15% of patients). These results suggest that reduced preoperative antifactor Xa activity has a low specificity for thrombosis after moderately extensive surgery in young, otherwise fit, oral contraceptive treated women. This test is therefore unlikely to be a clinically useful predictor for postoperative thrombosis in this group of patients.

Adolescent↗
PubMed1984

Thrombokinetics in patients with rheumatoid arthritis treated with D-penicillamine.

The mechanism of D-penicillamine induced thrombocytopenia in rheumatoid arthritis was investigated by measuring platelet life-span and platelet production rate in 2 groups of rheumatoid arthritis patients treated with 250-750 mg/day D-penicillamine, 14 with a normal platelet count and 9 with thrombocytopenia (platelet count 50-130 X 10(9)/1). Age matched control patients not treated with D-penicillamine included 14 with rheumatoid arthritis and 9 with osteoarthritis. The platelet life-span was normal, but platelet production rate was significantly reduced in the thrombocytopenic patients, suggesting that D-penicillamine causes thrombocytopenia through bone marrow suppression.

Adult↗
PubMed1982

The effect of sulphinpyrazone on oxidative drug metabolism in man: inhibition of tolbutamide elimination.

The effect of sulphinpyrazone on tolbutamide elimination was investigated in 6 healthy male volunteers. Co-administration of sulphinpyrazone (200 mg, 6 hourly) reduced mean plasma tolbutamide clearance by 40% and prolonged mean tolbutamide half-life by 80%. Twenty four hours after the cessation of a one week period of chronic sulphinpyrazone therapy tolbutamide plasma clearance (30% reduction) and half-life (19% prolongation) were still significantly different to control values, even though sulphinpyrazone could not be detected in the plasma of any of the subjects at this time. In vitro studies of the plasma protein binding of tolbutamide demonstrated concentration dependent binding but displacement of tolbutamide by sulphinpyrazone in vitro only became apparent at high concentrations of added sulphinpyrazone. Although the concentration dependence of tolbutamide protein binding demonstrated in vitro was also observed in the subject plasma samples, the magnitude of this effect was small. It is concluded that sulphinpyrazone and its metabolite(s) decrease the plasma clearance of tolbutamide by inhibition of oxidative metabolism.

Adult↗
PubMed1982

Interaction of sulphinpyrazone with warfarin.

The effect of sulphinpyrazone administration on the anticoagulant response was investigated in five patients receiving long-term treatment with warfarin. Sulphinpyrazone caused a rapid increase in prothrombin (PT) ratio in all five patients and warfarin dose had to be reduced by a mean of 46% to maintain the PT ratio in the therapeutic range. PT ratio and daily warfarin requirement returned to previous levels when sulphinpyrazone was ceased. Warfarin protein binding was not altered during sulphinpyrazone administration and sulphinpyrazone added to plasma in vitro did not increase warfarin free fraction. The average racemic plasma warfarin concentration over a dosage interval when adjusted for warfarin dose was not altered by sulphinpyrazone administration. The most likely mechanism for this drug interaction is a stereoselective effect of sulphinpyrazone on the metabolism of the warfarin enantiomers.

Aged↗
PubMed1982

Anticoagulants: the state of the art.

Some aspects of the use of anticoagulants to prevent or treat thromboembolic disorders remain controversial after more than 40 years of clinical trial and experience. This review describes the mode of action of heparin and the oral anticoagulants and examines their practical use for the prevention and treatment of venous thromboembolism.

Administration, Oral↗
PubMed1980

The relevance of platelet and fibrinogen kinetics and coagulation studies to extent of disease and performance status in patients with adenocarcinoma.

In this study of 18 cancer patients, results of laboratory evaluation of a "hypercoagulable state" have been correlated with the extent of the disease and the functional activity of the patients. Most coagulation tests were normal. Higher levels of serum fibrinogen degradation products were associated with wider dissemination of disease. Fibrinogen survival time (t1/2) was shorter in patients with extensive disease than in those with less extensive disease (P < 0.05); platelet t1/2 was also shorter in the former group, though not significantly. Coexistence of severest physical disability and extensive disease was associated with the most marked reduction of platelet and fibrinogen t1/2. There was little correlation between platelet and fibrinogen t1/2, thus suggesting independent mechanisms of destruction of the two blood components. We suggest that future studies of hemostatic changes in cancer patients should include assessment of impairment of physical performance of the patients, as well as the extent of the tumor.

Adenocarcinoma↗
PubMed1980

Heparin-associated thrombocytopenia: case report and prospective study.

After observing a patient with heparin-induced thrombocytopenia we prospectively recorded the incidence of thrombocytopenia associated with heparin treatment by measuring the platelet count every second day in 166 patients given therapeutic heparin for various thromboembolic disorders, and 51 patients given low-dose heparin prophylaxis. A platelet count below 100 x 10(9)/litre developed in nine patients (5.4%) during or soon after full-dose heparin therapy, and in one patient given low-dose heparin. Careful clinical review suggested that heparin was either the most likely cause of a contributing cause of thrombocytopenia in 5/166 patients (3.0%) receiving therapeutic heparin and none of the patients who received prophylactic heparin. Associated laboratory studies suggest that heparin-initiated platelet aggregation in vivo is a useful marker for heparin-induced thrombocytopenia.

Adult↗