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J Stibbe

Publications and source records attributed to J Stibbe.

At least 19 recordsLinked to original sources
PubMed1992

Increased tissue-type plasminogen activator activity in orthotopic but not heterotopic liver transplantation: the role of the anhepatic period.

The major cause of the increased tissue-type plasminogen activator activity during orthotopic liver transplantation is still unclear. Both the lack of hepatic clearance of tissue-type plasminogen activator in the anhepatic period and increased endothelial release from the graft on reperfusion have been proposed as the major causes. Heterotopic liver transplantation avoids the resection of the host liver and is a useful model to help differentiate between these two possibilities. In this study the fibrinolytic system was evaluated in 10 orthotopic liver transplantations, 18 heterotopic liver transplantations and a control group of 10 partial hepatic resections. A marked increment in tissue-type plasminogen activator activity, from 0.2 to 5.2 IU/ml (p less than 0.02), was observed during the anhepatic period of orthotopic liver transplantation, which rapidly normalized after reperfusion. In contrast, tissue-type plasminogen activator activity levels remained normal in heterotopic liver transplantation and partial hepatic resections. In orthotopic liver transplantation and in heterotopic liver transplantation no increase occurred in tissue-type plasminogen activator activity after reperfusion. The first venous hepatic outflow after reperfusion did not contain elevated tissue-type plasminogen activator activity levels. Plasma degradation products of fibrin and fibrinogen increased during the anhepatic period of orthotopic liver transplantation (from 2.60 to 8.80 micrograms/ml [p less than 0.008] and from 0.40 to 1.60 micrograms/ml [p less than 0.04], respectively) and remained elevated thereafter. In heterotopic liver transplantation and partial hepatic resections these levels remained low. In conclusion, the lack of hepatic clearance during the anhepatic period is probably the most important factor in the evolution of increased tissue-type plasminogen activator activity during orthotopic liver transplantation.

Blood Transfusion↗
PubMed1992

Disseminated intravascular coagulation in liver cirrhosis.

UNLABELLED: We measured thrombin-antithrombin III complex (TAT), soluble fibrin (SF) and D-dimer levels in 51 patients with liver cirrhosis to determine whether these tests provide new evidence for the presence of disseminated intravascular coagulation (DIC) in liver cirrhosis. TAT levels (median, range) were increased in the patient group (4.2 micrograms/l, 1.8-60.0) compared to the reference group (2.0 micrograms/l, range 1.5-7.6 micrograms/l). SF levels (0 nmol/l, range 0-80 nmol/l) were also increased in the patients as compared to the controls (0 nmol/l, 0), but there was no correlation between TAT and SF levels (r = 0.23, p less than 0.98). TAT levels did not correlate with AT-III levels (r = -0.36, p less than 0.49), but there was an inverse correlation between SF and AT-III (r = 0.60, p less than 0.001). If AT-III levels were above 0.30 U/ml, SF levels remained low, whereas SF levels were increased in patients with AT-III levels below 0.30 U/ml. These findings suggest that if sufficient AT-III is present, thrombin formation is adequately controlled, whereas at low levels of AT-III, thrombin escapes inactivation by AT-III and may act upon fibrinogen, leading to the formation of SF and a low-grade DIC. SF levels correlated well with D-dimer levels (r = 0.55, p less than 0.001), which is consistent with DIC and secondary fibrinolysis. IN CONCLUSION: (1) thrombin formation is increased in liver cirrhosis, as indicated by increased TAT levels in 21 of 51 patients; (2) the plasma concentration of AT-III appears to be of major importance for the development of DIC. The present study provides evidence for DIC in severe liver cirrhosis when AT-III levels are less than 0.30 U/ml.

Adult↗
PubMed1991

Prevention of restenosis after percutaneous transluminal coronary angioplasty with thromboxane A2-receptor blockade. A randomized, double-blind, placebo-controlled trial. Coronary Artery Restenosis Prevention on Repeated Thromboxane-Antagonism Study (CARPORT).

BACKGROUND: GR32191B is a novel thromboxane A2-receptor antagonist with potent antiagregational and antivasoconstrictive properties. We have conducted a randomized, double-blind placebo-controlled trial to study its usefulness in restenosis prevention. METHODS AND RESULTS: Patients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo for 6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was -0.31 +/- 0.54 mm in the control group and -0.31 +/- 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-to-treat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free. CONCLUSIONS: Long-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1990

[Possibilities and limitations of heterotopic auxiliary liver transplantation].

Although auxiliary heterotopic liver transplantation offers theoretical advantages over orthotopic liver replacement, clinical results have heretofore been dismal. After development of a technique of reduced size liver grafts provided with portal and arterial blood and venous drainage via the suprahepatic V. cava (HLT) in experimental animals, this method was applied in 21 transplantations in 19 patients. 11 of 16 patients with chronic liver insufficiency and one of three patients with fulminant liver failure survived transplantation for at least 1 year. HLT was well tolerated even by high-risk patients. Possibilities and limitations of this novel approach are discussed.

Adult↗
PubMed1990

Biochemical and behavioral responses of pilocarpine at muscarinic receptor subtypes in the CNS. Comparison with receptor binding and low-energy conformations.

Pilocarpine was tested biochemically in vitro for its ability to stimulate phosphoinositide (PI) turnover in the hippocampus (M1/M3 responses) where it displayed 35% of the maximal carbachol response with an EC50 value of 18 microM, and low-Km GTPase in the cortex (M2 response), where it had 50% of the maximal carbachol response with an EC50 value of 4.5 microM. Behaviorally, pilocarpine was able to restore deficits in a representational memory task (sensitive to M1 antagonists) produced by intrahippocampal injections of AF64A. Twenty-three low-energy conformations of protonated pilocarpine were generated using the program MacroModel. The data indicate that pilocarpine is a partial agonist at both M1 and M2 muscarinic receptors in the CNS. Behaviorally, with respect to the memory task, M1 effects of pilocarpine apparently predominate. It also is conceivable that different conformations of pilocarpine are active as agonists at different muscarinic receptor subtypes.

Animals↗
PubMed1990

Evidence for a preferential involvement of M1 muscarinic receptors in representational memory.

The effects of intrahippocampal injections to the M1-selective antagonist pirenzepine and the M2-selective antagonist AF-DX 116 were examined on performance of a representational memory task in rats. Although both antagonists impaired performance, pirenzepine was more potent than AF-DX 116. Pirenzepine (70.8 +/- 2.8% correct) produced a greater deficit than AF-DX 116 (83.3 +/- 0.0%) at 70 micrograms, and the deficit at 10 micrograms (83.3 +/- 2.8%) was equal to that produced by 70 micrograms of AF-DX 116. The data provide additional support for the cholinergic hypothesis of memory and new information regarding the subtypes of muscarinic receptors likely to be involved in representational memory. Based on the greater susceptibility of representational memory to the effects of pirenzepine, it is suggested that M1 receptors in the hippocampus play a greater role in memory function than M2 receptors.

Animals↗
PubMed1990

Haemophilia protects against ischaemic heart disease: a study of risk factors.

We previously reported that mortality due to ischaemic heart disease was lower in haemophilia patients than in the general male population. To support the hypothesis that this could be attributed to a protective effect of the clotting defect in haemophilia and not to differences in cardiovascular risk factors, we performed a second study. We examined 95 haemophilia patients for the presence of major risk factors for ischaemic heart disease and compared their risk factor profile with the data of epidemiologic surveys of the general Dutch population. Haemophilia patients had on average higher blood pressures than the comparison population, were more often hypertensive and used antihypertensive drugs twice as often. The mean serum cholesterol level of the patients was markedly lower than in the comparison population (4.8 versus 5.6 mmol/l, 95% confidence interval of the difference: 0.5-1.1 mmol/l). The risk factors were weighted into one theoretical risk ratio for ischaemic heart disease by application of logistic regression coefficients. The theoretical risk ratio based on the risk factor profile was 0.78. This risk ratio can only explain a moderate reduction in the incidence of ischaemic heart disease, much smaller than the mortality ratio of 0.20 we reported previously. Therefore these data support the hypothesis of a direct protective effect of haemophilia on the development of ischaemic heart disease.

Adolescent↗
PubMed1990

Normal homeostasis of fibrinolysis in nephrogenic diabetes insipidus in spite of defective V2- receptor-mediated responses of tissue plasminogen activator release.

Three patients with congenital, nephrogenic diabetes insipidus (NDI) from two unrelated families were tested for haemostatic and fibrinolytic responses to DDAVP infusion and venous occlusion. None of the three patients showed a response of factor VIII:C, vWF:Ag or t-PA to DDAVP, a V2-agonist. However, the baseline levels of these factors in the patients' plasma were normal and during venous occlusion a rise in t-PA antigen and t-PA activity was observed in all patients. One patient showed a definite response of the t-PA antigen level to exercise. It is concluded that (extrarenal) V2-receptor-mediated responses are absent in these patients, but that baseline homeostasis and the response to venous occlusion and physical exertion are intact. Presumably, these depend on other mechanisms. This observation denies a central role for vasopressin receptors in the on-demand regulation of clotting and clot dissolving properties of the blood.

Adult↗
PubMed1990

Selection of asymptomatic HIV carriers for antiviral therapy.

In order to find suitable markers for selection and monitoring of antiviral therapy in asymptomatic HIV-infected patients, we evaluated 18 anti-HIV positive individuals at three monthly intervals by HIV culture, HIV antigen, and core (p24) antibody testing as well as by measurement of lymphocyte subsets. Consistent results were obtained with HIV antigen, p24 antibody testing and T4 cell enumeration, whereas results of virus detection were variable. Therefore cumbersome and expensive virus culture is not of use in selecting patients for antiviral therapy. On the basis of our results and recent literature we currently propose using absence of p24 antibodies, presence of HIV antigen and low or falling T4 cells as eligibility criteria for antiviral therapy in asymptomatic infected individuals.

Antiviral Agents↗
PubMed1988

Fatal ischaemic brain oedema after early thrombolysis with tissue plasminogen activator in acute stroke.

Two patients with acute major, disabling cerebral infarction with presumed middle cerebral artery occlusion were treated with the clot specific thrombolytic agent tissue plasminogen activator roughly three and a half hours after the onset of symptoms. Both patients had a normal computed tomography (CT) scan before treatment. No appreciable systemic bleeding complications occurred, apart from bruising. One patient had bleeding into the subarachnoid space from a microscopic angioma, which was found at necropsy. Haematological monitoring of the two patients showed pronounced fibrinogenolysis and alpha 2 antiplasmin consumption in one. One patient showed transient improvement during the infusion. In both cases extensive infarction, partly haemorrhagic in one, with massive concomitant oedema was found on repeated CT. Both patients deteriorated and eventually died as a consequence of transtentorial herniation. In the one patient who came to necropsy a moderate, probably pre-existing smooth stenosis of the ipsilateral carotid artery was found, all cerebral vessels being patent. It is concluded that thrombolytic treatment with a clot specific agent such as tissue plasminogen activator started three to four hours after a major ischaemic stroke may be hazardous, not because of haemorrhagic transformation of the original ischaemia but because early reperfusion may promote massive, potentially fatal cerebral oedema.

Acute Disease↗
PubMed1988

Mild haemostatic problems associated with congenital heterozygous alpha 2-antiplasmin deficiency.

A Dutch family, of which 13 members are heterozygotes, deficient for alpha 2-antiplasmin (alpha 2-AP) is reported. Clinical studies showed that 2 heterozygotes had a mild bleeding tendency, which presented as bleeding episodes after tooth extraction and after surgery and, in one patient, also as excessive menstruation. Laboratory investigations revealed an alpha 2-AP activity of 62% (51-71) (median and range) and an antigen level of 60% (60-66). The plasminogen binding as well as the fibrin binding properties of alpha 2-AP were normal. Plasminogen concentrations were significantly higher in the heterozygotes compared to the other family members. However, free plasminogen not bound to histidine-rich glycoprotein was not significantly different between these two groups. We propose that in this family the deficiency of alpha 2-AP is due to a decreased synthesis of a normal alpha 2-AP molecule. This present study brings the frequency of heterozygous alpha 2-AP deficient patients with a bleeding tendency to 13 out of 59 heterozygotes reported in the literature.

Adult↗
PubMed1988

Prevention of thrombosis after hip arthroplasty. A prospective study of preoperative oral anticoagulants.

A prospective randomized study involving 101 patients undergoing total hip replacement was performed to find out whether prophylactic anticoagulation starting 4 days before the operation was more effective than starting on the eve of the operation. The postoperative level of anticoagulation was set at an INR of 2.1. There was no difference between the two groups in the incidence of proximal localized deep venous thrombosis. Blood loss did not depend on the level of peroperative anticoagulation. There were no postoperative hemorrhagic complications. No fatal pulmonary embolism occurred during the study. After discontinuation of the oral anticoagulants because of a negative venogram, nonfatal pulmonary embolism occurred in 3 out of 55 patients. A plea is made for low-dose anticoagulation for 3 months after total hip arthroplasty.

Acenocoumarol↗
PubMed1987

Effectiveness of long term oral anticoagulation treatment in preventing venous thrombosis in hereditary protein S deficiency.

In eight of 14 patients who were deficient in protein S and who belonged to two unrelated families thrombosis presented as thrombophlebitis in seven and deep vein thrombosis in six, complicated by pulmonary embolism in four and leg ulcers in two. In four patients superficial thrombophlebitis preceded deep vein thrombosis by one to 11 years. Post-thrombotic varicose veins and venous insufficiency had developed in four patients. In three of those and in a fourth patient symptomatic superficial thrombophlebitis, deep vein thrombosis, and pulmonary embolism did not recur while they were taking oral anticoagulant treatment for six to 12 years. The anticoagulation intensity corresponded to international normalised ratio values of over 2.5. It is concluded that the benefits of anticoagulant treatment for patients with congenital thrombotic disease are great, and thus it is necessary to make an early diagnosis and treat patients at risk of developing thrombosis.

Administration, Oral↗