Search PubMed⌕ Search

Biomedical subjects

W F Lubbe

Publications and source records attributed to W F Lubbe.

At least 37 records · Page 2Linked to original sources
PubMed1985

Lupus anticoagulant and pregnancy.

A subset of women with a high rate of fetal wastage is identifiable among those with serologic but not necessarily clinical evidence of connective tissue disease. The presence of lupus anticoagulant in the plasma of a pregnant woman serves as a marker for a high rate of fetal wastage and risk of thrombosis. Lupus anticoagulant is best identified by the activated partial thromboplastin time or kaolin clotting time and can be specifically confirmed by the platelet neutralization procedure. Review of the obstetric literature indicates a total of 49 women with 160 unsuccessful pregnancies and 13 live births. Prednisone in immunosuppressive doses (40 to 60 mg/day) combined with low-dose aspirin (75 mg/day) has been demonstrated to be effective in suppressing activity of lupus anticoagulant in pregnant women and successful pregnancies have been obtained with this treatment. Lupus anticoagulant should be excluded in women with suspected collagen disease, with repeated early abortions and all unexpected late fetal losses.

Aspirin↗
PubMed1984

Lupus anticoagulant in pregnancy.

In a group of 10 women with circulating lupus anticoagulant 25 intrauterine deaths were previously documented in the nine multigravidae. The presence of lupus anticoagulant activity was confirmed by showing prolongation of the activated partial thromboplastin time and kaolin clotting time with failure of correction of the prolongation on incubation with normal plasma. A clinical diagnosis of systemic lupus erythematosus (SLE) was made in four women. Three had deep vein thrombosis in pregnancy, one chorea gravidarum while two had only recurrent fetal losses. All the women had positive antinuclear antibody tests and blood platelet counts less than 175 X 10(9)/l. Anti-smooth muscle antibody and VDRL tests were each positive in half the patients; anti-DNA antibody was present in two patients with clinically active SLE. In six pregnancies correction of the activated partial thromboplastin and kaolin clotting time was attempted using prednisone (40-60 mg/day); aspirin, 75 mg/day, was added. Five live infants were obtained, four by spontaneous delivery, when the restoration of the clotting abnormalities to normal was achieved. In one woman presenting with extensive deep vein thrombosis a live infant was delivered following therapeutic doses of heparin and low dose aspirin. Maternal lupus anticoagulant activity has major implications for pregnancy and should be excluded in women with a clinical suspicion of SLE, a positive antinuclear antibody test, thrombotic episodes, biologically false-positive VDRL and unexplained late or repetitive early fetal losses.

Aspirin↗
PubMed1984

Hypertension in pregnancy. Pathophysiology and management.

Hypertension in pregnancy has implications for both maternal and fetal welfare. Extrapolation from concepts of mechanisms operating in hypertension in general to pregnancy-related hypertension is not justified. In the latter, the major features are a hyper-adrenergic state, plasma volume reduction and an increased systemic resistance. A reduction in uteroplacental perfusion may result from or may activate the mechanisms that elevate blood pressure. Humoral factors (e.g. hormonal attenuation of vascular reactivity) and prostacyclin deficiency may be central to the disordered physiology. Treatment of hypertension in pregnancy should aim at avoiding the vascular damage due to blood pressure elevation but not cause a reduction in uteroplacental perfusion. Unlike earlier antihypertensive regimens using centrally acting sympatholytics, adrenergic neuron blockers or diuretics, regimens using beta-blockers or combinations of beta-blockers with alpha-blockers or vasodilating agents such as hydralazine permit effective blood pressure control, even in severe hypertension, and pregnancy can often proceed until term or until fetal maturity is secured. Adverse effects on the fetus (growth retardation, cardiorespiratory depression, hypoglycaemia, hyperbilirubinaemia) formerly attributed to beta-blockers are more likely related to poorly controlled hypertension. Specific benefits of maternal beta-adrenoceptor blockade are suggested by evidence for prevention of proteinuric deterioration and a decrease in the incidence and severity of respiratory distress in premature infants. Hypertension in pregnancy still presents a formidable therapeutic challenge and requires comprehensive management with close monitoring of fetal welfare. The presence or development of proteinuria in a hypertensive pregnant woman implies a major increase in risk to the fetus and warrants immediate admission to hospital for specialist management.

Adrenergic alpha-Antagonists↗
PubMed1983

Fetal survival after prednisone suppression of maternal lupus-anticoagulant.

The presence of the lupus anticoagulant was diagnosed in six pregnant women because they had prolonged activated partial thromboplastin and kaolin clotting times which could not be corrected by dilution of test samples with normal plasma. All previous pregnancies (14) had ended in intrauterine death in the five multigravidas. Three women had had thrombotic episodes during pregnancy. The diagnosis of SLE was established in four. Antinuclear antibody was identifiable in all 6. All were treated with prednisone 40-60 mg/day and aspirin 75 mg/day. Suppression of the lupus anticoagulant activity was achieved in five patients, all of whom gave birth to live infants. In the sixth patient suppression of the anticoagulant activity was demonstrated between pregnancies; a further pregnancy in this patient was lost before she had received sufficient prednisone to suppress the anticoagulant. Since treatment with prednisone and aspirin can lead to successful pregnancies, it is important to screen all women with SLE, thrombotic episodes, recurrent intrauterine deaths, or a biologically false-positive VDRL for the presence of the lupus anticoagulant.

Adult↗
PubMed1983

Modulation of myocardial cyclic AMP and vulnerability to fibrillation in the rat heart.

In the isolated rat heart, changes in the ventricular fibrillation threshold (VFT) relate to the myocardial cyclic AMP content rather than to the high-energy phosphate content. After coronary ligation the reduction in VFT correlates with the increase in ischemic tissue cyclic AMP. Agents that reduce the myocardial cyclic AMP (propranolol, 16 microM in perfusate, or amiodarone, 42 microM/kg pretreatment) prevent the postligation fall of the VFT without altering high-energy phosphate depletion. Conversely, theophylline (500 microM), which increases cyclic AMP in ischemic myocardium, causes a greater reduction of VFT without increasing high-energy phosphate depletion. Spontaneous ventricular tachycardia and fibrillation are uncommon in coronary ligated hearts in the first 15 min after ligation (10-20%); these arrhythmias are greatly increased either by reducing the perfusate potassium from 5.9 to 3.0 mM or by pretreating hearts with 1-methyl-3-isobutyl xanthine (10 microM), a cyclic-AMP phosphodiesterase inhibitor. Adenosine (100 microM) antagonizes the increased arrhythmogenesis in both low perfusate potassium and cyclic-AMP phosphodiesterase-inhibited hearts, in the latter without reducing the ischemic tissue cyclic AMP levels. The antiarrhythmic action of adenosine in these hearts is independent of reducing tissue cyclic AMP. Adenosine generated in ischemic myocardium may serve as an endogenous antagonist to the arrhythmogenic action of cyclic AMP.

Adenosine↗
PubMed1983

Beneficial effect of labetalol in hypertensive patients with angina pectoris.

Labetalol (Trandate; Allen & Hanbury) was administered to 17 hypertensive patients with angina pectoris, which had persisted despite blood pressure control on treatment including beta-blocking agents. In comparison with placebo, labetalol significantly reduced the frequency and severity of attacks of angina pectoris, without further improvement in control of blood pressure at rest, during isotonic exercise or on performance of the cold pressor test. Labetalol significantly reduced blood pressure levels during isometric exercise but did not reduce the systolic pressure- heart rate product. Labetalol improved the angina without evidence of causing a reduction of cardiac work (and presumably oxygen consumption by the myocardium) in comparison with the other antihypertensive agents used in this study. A possible mechanism whereby labetalol increases myocardial blood supply in hypertensive patients with angina pectoris is by an increase in coronary perfusion due to its vasodilator action.

Adult↗
PubMed1983

Antiarrhythmic action of labetalol and its effect on adenine metabolism in the isolated rat heart.

Labetalol, a combined alpha- and beta-adrenergic antagonist, was assessed for antiarrhythmic activity in the isolated perfused rat heart. Inclusion of 5.0 and 7.5 mumol/liter labetalol in the perfusate reduced the fall in ventricular fibrillation threshold and eliminated ventricular arrhythmias during the coronary occlusion period of 15 minutes. In treated hearts, levels of high energy phosphates were significantly higher and lactate, adenosine and hypoxanthine levels were lower in ischemic myocardium. Cyclic adenosine monophosphate levels were reduced in uninvolved myocardium (0.31 +/- 0.01 and 0.24 +/- 0.02 versus 0.43 +/- 0.02 nmol/g fresh weight) and in the ischemic myocardium (0.38 +/- 0.02 and 0.34 +/- 0.04 versus 0.65 +/- 0.05 nmol/g) in hearts treated respectively with 5.0 and 7.5 mumol/liter labetalol versus control hearts. When untreated hearts were perfused with 3.0 mmol/liter potassium in perfusate, all had ventricular tachycardia or fibrillation during coronary ligation and developed ventricular fibrillation after reperfusion. Labetalol, 5.0 mumol/liter, reduced ventricular tachyarrhythmias during coronary occlusion and after reperfusion, whereas labetalol, 7.5 mumol/liter, eliminated tachyarrhythmias during occlusion and reperfusion. Labetalol had potent antiarrhythmic activity in the hearts rendered uniformly prone to arrhythmias by perfusion with a low potassium solution.

Adenine↗
PubMed1983

What has the baboon to offer as a model of experimental ischemia?

The greatest advantage of the baboon model is the phylogenetic closeness of the animal to man which may be of considerable importance when dealing with receptor-related events and with drug-specific therapy. The major disadvantage is the difficulty of dealing with awake baboons and the absence of any adequate model for coronary artery spasm.

Animals↗
PubMed1982

Hepatic and splenic haemorrhage as a complication of toxaemia of pregnancy in a patient with circulating lupus anticoagulant.

A 29 year old pregnant woman presented at 28 weeks with severe upper abdominal pain. Features of pre-eclamptic toxaemia became apparent and intrauterine death occurred abruptly. The development of shock, a reduction in haemoglobin from 124 to 88 g/l without evidence of external blood loss and tender hepatosplenomegaly suggested major intrahepatic and intrasplenic haemorrhage. This suggestion was supported by ultrasound and CT scans. The patient made a complete recovery over a period of weeks. She was shown to have a circulating LE-inhibitor and had major thrombotic episodes involving her leg veins.

Adult↗