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Biomedical subjects

J Swedenborg

Publications and source records attributed to J Swedenborg.

At least 37 records · Page 2Linked to original sources
PubMed1998

The mechanisms of action of alpha- and beta-isoforms of antithrombin.

Antithrombin (AT) is the most important physiological inhibitor of thrombin. This effect can be increased more than a 1000-fold by heparin and heparin-like glycosaminoglycans, which induce a conformational change in the molecule. Two isoforms of AT exist in plasma: alpha and beta. The beta-isoform lacks one of four carbohydrate side-chains that are present on the alpha-isoform. The beta-isoform, which constitutes approximately 10% of plasma AT, has a higher affinity for heparin and heparin-like glycosaminoglycans than the alpha-isoform. In contrast to their distribution in plasma, the two isoforms of AT appear to be present in the same proportions in the vessel wall. After balloon injury of rabbit aorta, thrombin can be detected in the vessel wall, an effect that is inhibited by treatment with AT. The inhibitory effect of AT on thrombin coagulant activity in the injured vessel wall is attributable to the beta-isoform. The appearance of thrombin in the injured vessel wall can also be inhibited by heparin treatment, but this requires heparin to be circulating in plasma at the time of excision of the injured vessel wall. Thrombin has been suggested as a mitogen for smooth muscle cells. This effect of thrombin can be inhibited by AT, an inhibition that is increased by heparin in a concentration-dependent manner. The alpha-isoform of AT has a lower inhibitory capacity for the thrombin-induced proliferation of smooth muscle cells in the absence of heparin, compared with the beta-isoform, which is an effective inhibitor alone. This indicates that the beta-isoform of AT may use glycosaminoglycans produced by smooth muscle cells as a cofactor. In conclusion, the beta-isoform of AT appears to be an effective inhibitor of the thrombin coagulant activity induced by vessel wall injury. It is also a more effective inhibitor of the thrombin-induced proliferation of smooth muscle cells than the alpha-isoform.

Animals↗
PubMed1998

Activation of tissue-factor gene expression in breast carcinoma cells by stimulation of the RAF-ERK signaling pathway.

Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the extrinsic pathway of coagulation. The overexpression of TF in human malignancy has been correlated with the angiogenic phenotype, poor prognosis, and thromboembolic complications. The mechanisms underlying constitutive expression of TF in cancer cells are poorly defined. We cloned TF cDNA on the basis of its strong expression in metastatic MDA-MB-231 breast carcinoma cells in contrast to its weak expression in non-metastatic MCF-7 cells. Transient transfection analysis showed that TF promoter activity in MCF-7 cells could be stimulated by expression of a membrane-targeted raf kinase (raf-CAAX). raf-induced activity was dependent on the presence of an AP-1/NF-kappaB motif in the TF promoter and was inhibited by dominant-negative mutants of jun and by I-kappaB alpha. MDA-MB-231 cells were found to contain higher levels of ERK1/2 kinase activity than did MCF-7 cells. Electrophoretic mobility shift assays showed that MDA-MB-231 nuclear proteins bound strongly to an oligonucleotide corresponding to the AP-1/NF-kappaB sequence, whereas MCF-7 nuclear extracts showed weak binding to this element. Finally, we showed that TF mRNA levels in MDA-MB-231 cells declined after addition of the mitogen-activated protein kinase kinase inhibitor PD98059. Our data showed that activation of the raf-ERK pathway led to activation of TF expression in breast carcinoma cells and suggested that constitutive activation of this pathway leads to high TF expression in MDA-MB-231 cells.

Base Sequence↗
PubMed1997

In vitro endothelialisation of arteriovenous loop grafts for haemodialysis.

OBJECTIVES: To evaluate the feasibility in a pilot study of in vitro endothelialisation of PTFE grafts used as interposition arteriovenous fistulas in uraemic patients. METHODS: Autologous saphenous vein endothelial cells were harvested and cultured on PTFE grafts in seven patients undergoing maintenance haemodialysis. The patients had several previous failures of vascular access sites. The patients were followed with duplex ultrasound, clinical examination and in one case an explanted graft was examined. RESULTS: At the end of follow-up four of the seven patients had patent grafts. One patient occluded the graft immediately postoperatively and another after 3.5 months. The former patient received a second endothelialised graft. In two further patients revision of the outflow was performed. In two patients a functioning graft was excised, in one case because of bleeding of a venous aneurysm and in one case because of suspected infection. The former which was excised 5 weeks postoperatively revealed that 85% of the surface was covered by endothelial cells. CONCLUSIONS: This pilot study shows that in vitro endothelialisation of PTFE grafts used for haemodialysis is possible in uraemic patients. In this highly problematic patient group the results are promising with endothelial cell coverage after 5 weeks of implantation.

Aged↗
PubMed1997

The efficacy of transfemoral endovascular aneurysm management: a study on size changes of the abdominal aorta during mid-term follow-up.

OBJECTIVES: The aim of this study was to assess efficacy of transfemoral endovascular aneurysm management (TEAM) during mid-term follow-up. DESIGN: Prospective multicentre study. MATERIALS AND METHODS: In 26 patients treated by a Tube Endograft, the pre- and postoperative contrast enhanced computed tomography (CT) images were reviewed in a blinded fashion. Aortic diameters were measured at the coeliac trunk, the inferior and superior aneurysm neck and the level of the maximal aneurysm size. The changes in diameter were related to the presence or absence of an endoleak. RESULTS: The median follow-up was 12 months. In 10 patients an endoleak was found. Three endoleaks sealed spontaneously within 30 days after operation. All aneurysms with persistent endoleaks expanded, at a median rate of 0.30 mm per month. Four patients were converted between 9 and 14 months after TEAM. Aneurysms excluded by the endoprosthesis showed a median shrinkage of 0.41 mm per month. The inferior aneurysm neck demonstrated significant growth during follow-up, unrelated to endoleaks. CONCLUSIONS: This study demonstrated the efficacy of TEAM in discontinuing the process of aneurysm expansion. Complete seal of the aneurysm sac after TEAM leads to shrinkage or arrest of growth of the aneurysm, while persistent endoleak is associated with progressive expansion.

Aged↗
PubMed1997

Heparin-chitosan complexes stimulate wound healing in human skin.

The effect of heparin ionically linked to chitosan on the stimulation of re-epithelialisation of full thickness wounds in human skin was investigated in an in vitro model. After seven days of incubation, heparin-chitosan gel stimulated 9/10 of the full thickness wounds to re-epithelialise compared with only 3/10 of the wounds that were covered with chitosan gel or membrane, and none of the wounds incubated without gel or membrane or with heparin solution alone. Both dermal and epidermal cells were viable after the incubation time. Furthermore, the stimulatory effect of the heparin-chitosan complexes depended on the concentration of heparin in the complex. We hypothesise that these effects are caused by stabilisation and activation of growth factors that bind to immobilised heparin.

Biocompatible Materials↗
PubMed1996

Early experience with transfemoral endovascular aneurysm management (TEAM) in the treatment of aortic aneurysms.

OBJECTIVES: To evaluate the early experience with transfemoral endovascular aortic aneurysm management using the Endovascular Grafting System. DESIGN: Multi-centre prospective evaluation of the implantation procedure and early results (median follow-up 153 days). SETTING: Department of Surgery, University Hospital Utrecht, The Netherlands; Department of Surgery, University of Sydney, Australia; University of Leicester School of Medicine, Leicester, U.K., Department of Surgery, Karolinska Hospital, Stockholm, Sweden and Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital; Oxford, U.K. MATERIALS: 31 consecutive patients treated in 13 months. CHIEF OUTCOME MEASUREMENTS: Peri and postoperative morbidity and mortality in accordance with the recommendations of the Ad Hoc Committee on Reporting Standards. MAIN RESULTS: Graft placement was initially successful in all 31 patients. In one patient the endograft had to be replaced by a standard aortic tube graft because of extra graft flow in the aneurysm sac, and complaints of back pain. One patient died from multiple organ failure, 11 days after the operation. In three patients five severe adverse events were recorded. Breaks of the attachment system were encountered in two patients. These failures did not have severe clinical consequences for individual patients. CONCLUSIONS: Transfemoral Endovascular Aneurysm Management is a technically demanding procedure that requires special training in both catheter and surgical techniques. The potential for less operative morbidity when compared to conventional surgery and the prospect of technical improvements in graft and introduction system design will make TEAM an important tool in aneurysm management in the near future.

Aged↗
PubMed1996

Low molecular mass heparin instead of unfractionated heparin during infrainguinal bypass surgery.

OBJECTIVES: To test whether low molecular mass heparin (LMMH) is comparable to unfractionated heparin (UFH) as an anticoagulant during infrainguinal bypass surgery and to investigate laboratory evidence of hypercoagulation in patients undergoing infrainguinal bypass surgery. MATERIALS AND METHODS: Eighteen patients were randomised to receive either UFH or LMMH (70 anti-Xa units/kg b.w.). Soluble fibrin, measured as fibrin monomers (FM) and fibrinopeptide A (FPA), were measured in blood from the femoral vein before, during and after release of the occluding clamps during surgery. In addition, fibrinogen prothrombin complex, thrombin-antithrombin complex, platelets and antithrombin were measured before surgery. Heparin levels (Anti Xa) were measured during surgery. RESULTS: Increased levels of fibrinogen, FPA, thrombin antithrombin complex and FM were recorded prior to surgery. During surgery no further increase was noted. The anti Xa levels were slightly higher in patients with LMMH than in patients receiving UFH. Levels of FM were significantly lower in patients receiving LMMH. No difference in FPA was noted. A positive correlation between fibrinogen and FPA and FM respectively was recorded. Four patients, two in each group, were reoperated for graft occlusion. One patient in the UFH group required reoperation because of bleeding. CONCLUSIONS: LMMH is comparable to UFH as an anticoagulant during infrainguinal bypass surgery. Variables reflecting hypercoagulability are elevated in this group of patients and are positively correlated to the fibrinogen level. High fibrinogen levels could thus be a risk for perioperative thrombosis.

Aged↗
PubMed1996

The long-term outcome of proximal vein thrombosis during pregnancy is not improved by the addition of surgical thrombectomy to anticoagulant treatment.

OBJECTIVES: To compare the long-term outcome for pregnant/puerperal women with iliofemoral venous thrombosis treated either with thrombectomy and additional anticoagulants or with anticoagulants alone. DESIGN: Retrospective study of two treatment methods. MATERIALS: Thirty women with iliofemoral venous thrombosis during pregnancy or puerperium were treated with thrombectomy and additional anticoagulants. Twenty-five women, with the same condition, treated with anticoagulants only were obtained from a registry. The mean follow-up time for both groups was 9 years. The patients of the two groups were well matched, had the same risk factor score and were comparable except for duration of symptoms before treatment. METHODS: The follow-up comprised history and clinical examination, colour Duplex ultrasound and venous strain-gauge plethysmography. RESULTS: Patency of iliac veins, symptoms of chronic venous disease, venous emptying and venous reflux did not differ between the groups. A significant reduction of outflow was found in 20% of the surgically treated patients and 16% of the controls. Impaired muscle pump function was seen in less than half of the patients in both groups. CONCLUSIONS: Surgical thrombectomy does not offer any advantage over anticoagulation treatment alone in the long-term outcome for patients with iliofemoral venous thrombosis during pregnancy or puerperium.

Adolescent↗
PubMed1996

Thrombin inhibition by antithrombin III on the subendothelium is explained by the isoform AT beta.

Balloon injury of the rabbit aorta results in thrombin coagulant activity on the injured vessel wall that causes fibrin formation. The anticoagulant activity of both the intact and injured vessel wall has been partly explained by glycosaminoglycans with heparin-like activity that augment that activity of antithrombin III (AT). AT exists in two isoforms, alpha and beta, AT beta, which constitutes only 5% to 10% of AT in plasma, lacks one carbohydrate side chain, has higher affinity for glycosaminoglycans, and associates more readily with the subendothelium. This study evaluated whether AT can inhibit thrombin on the injured vessel wall and, if so, whether one of the isoforms is more effective then the other. The two isoforms were isolated from human plasma by heparin-Sepharose chromatography, and the purity was investigated by isoelectric focusing and crossed immunoelectrophoresis. Rabbits were subjected to balloon injury of the aorta; 3 hours after injury the aorta was excised. Thrombin coagulant activity on the aorta was measured by exposure to fibrinogen and thereafter by measuring the generation of fibrinopeptide A. Injured animals were treated with AT, AT alpha, or AT beta and were compared with control animals. AT was demonstrated on the injured vessel wall by using an immunohistochemical method. Animals receiving crude AT had significantly lower amounts of thrombin coagulant activity on the injured aortic wall than control animals, but AT alpha at a comparable dose had no effect. AT beta was given in the same dose as crude AT and also at a dose (10%) proportional to its presence in plasma. Animals receiving AT beta had significantly lower values of thrombin on the injured aortic wall than control animals. We conclude that the inhibitory effect of AT on thrombin coagulant activity on the injured vessel wall in explained by its AT beta content.

Animals↗
PubMed1996

Cultured human endothelial cells seeded on expanded polytetrafluoroethylene support thrombin-mediated activation of protein C.

PURPOSE: Reduction of the thrombogenicity of synthetic vascular grafts by endothelialization has been suggested. The purpose of this study was to examine some of the non-thrombogenic properties of cultured adult human great saphenous vein endothelial cells seeded on expanded polytetrafluoroethylene (ePTFE) grafts. METHODS: Endothelialized grafts, control grafts, and wells were incubated with thrombin. Assays of thrombin loss from solution, thrombin coagulant activity, and protein C activation on the surface were obtained. The presence of thrombomodulin was confirmed with immunohistochemistry. RESULTS: Significantly more thrombin was found on the ePTFE grafts or wells that underwent endothelialization, and larger amounts were lost from the thrombin solution compared with the control group. Thrombin enzyme activity on the endothelialization group was almost completely represented by activation of protein C and only to a minor extent by activity towards fibrinogen. CONCLUSIONS: It is concluded that endothelial cells seeded on ePTFE retain the possibility to inhibit thrombin coagulant activity and to activate protein C. These findings provide support for the clinical applicability of cultured autologous endothelium on ePTFE grafts.

Adult↗
PubMed1996

Postocclusive reactive hyperemia estimating peripheral vascular resistance: a noninvasive method to predict outcome of infrainguinal vascular reconstructions?

OBJECTIVE: The peripheral vascular resistance is an important factor determining the outcome of infrainguinal revascularizations. When measured intraoperatively, it correlates to graft patency, but to select patients to surgery a preoperative, preferably noninvasive, method is necessary. The aim of the present study is to test if parameters recorded during postocclusive reactive hyperemia can be used for that purpose. EXPERIMENTAL DESIGN: This prospective study compares patients with occluded grafts within 30 days postoperatively to patients with patent grafts. SETTING: University Hospital. PATIENTS: Thirty patients with critical ischemia scheduled for infrainguinal bypass surgery. MEASURES: Correlations between intraoperatively measured peripheral resistance and preoperatively recorded parameters of postocclusive reactive hyperemia. The ability of the values to predict outcome. RESULTS: Peripheral resistance correlated significantly to two parameters during postocclusive reactive hyperemia recorded after thigh occlusion, flux reappearance time (r=0.47, p=0.01) and time to peak flux (r=0.41, p=0.03). Intraoperative peripheral resistance predicted graft occlusion at 30 days with a 90% accuracy, while parameters obtained during reactive hyperemia, only tended to predict adverse outcome. CONCLUSIONS: Several parameters during reactive hyperemia show weak correlation to intraoperatively measured peripheral resistance, but none was able to accurately predict graft failure. Further studies are needed to evaluate its capability for patient selection.

Aged↗
PubMed1995

Ruptured thoracic aortic aneurysms: a study of incidence and mortality rates.

PURPOSE: The purpose of this study was to determine the incidence and mortality rate of ruptured thoracic aortic aneurysm (TAA) in a well-defined population. METHODS: Retrospective analysis of complied data from multiple registries in Stockholm, Sweden was performed. RESULTS: Eighty-two and 76 cases were identified from 1980 and 1989, respectively, for an equal incidence of 5 per 100,000. Forty-one percent of the patients were alive on arrival at an emergency hospital, but the overall mortality rate was 97% to 100%. CONCLUSIONS: The mortality rate of ruptured TAA is high. To decrease this high mortality rate, efficient screening methods for the diagnosis of TAA must be worked out, characteristics indicating high risk of rupture must be identified, and efforts should be made to increase the number of operations for ruptured TAA.

Aged↗
PubMed1995

The "ad hoc" estimation of outflow does not predict patency of infrainguinal reconstructions.

OBJECTIVES: This prospective study was performed to evaluate the clinical implication of the adhoc estimation (also called SVS score) of outflow on patency of infrainguinal in situ femoropopliteal or -distal bypasses. METHODS: The bypasses were followed with Duplex scanning at 1, 3, 6, and 12 months after surgery. Fifty-three bypasses were recruited for the study, 20 of which were performed in 17 diabetics. In 47% the adhoc scoring was < or = 4.5 and in 53% it was between 5 and 10 (1 corresponds to an excellent outflow and 10 to a blind segment). RESULTS: Within the first 30 days eight occlusions occurred, all of which were surgically corrected. The adhoc score for these bypasses was 4.2 vs. 4.9 (NS) for those who did not occlude. During follow-up, revisions were performed in 21 cases (40%) with 30 interventions. At the end of 1 year, 68% of the bypasses were patent (80% among diabetics and 64% among non-diabetics, NS). Patency at 1 year was not influenced by the adhoc classification. CONCLUSION: The estimation of outflow from angiography seems to be of no value in predicting graft patency in infrainguinal grafting.

Adult↗
PubMed1995

Antibodies against endothelial cells and cardiolipin in young patients with peripheral atherosclerotic disease.

OBJECTIVES: To investigate the prevalence of anticardiolipin and antiendothelial cell antibodies in patients operated on for atherosclerotic peripheral vascular disease before 50 years of age. The hypothesis to be tested was whether antibodies associated with an immune/inflammatory damage to the vascular wall were associated also with early atherosclerosis. DESIGN: A case-control study. SETTING: Departments of surgery and an immunological research laboratory, and routine laboratories of two tertiary referral hospitals. SUBJECTS: All patients operated for atherosclerotic peripheral vascular disease before 50 years of age. Sixty-two patients (33 males, 29 females), and 67 age- and sex-matched controls participated. The diagnosis of atherosclerosis was made on the basis of the clinical presentation and angiographic visualization of the diseased vasculature. MAIN OUTCOME MEASURES: Subjects were compared for the prevalence of anticardiolipin and antiendothelial cell antibodies, altered serum lipoprotein levels, smoking, diabetes, hypertension, and signs of inflammation. RESULTS: Antibodies against endothelial cells and cardiolipin were found in 12.9 and 14.5% of the patients, respectively, which was higher than observed in the control group (P < 0.05). Sixty per cent of patients with antibodies were females. Conventional risk factors were more often noted in the patient group. However, patients with antibodies against endothelial cell and/or cardiolipin had a lower prevalence of hyperlipidaemia/dyslipidaemia when compared to patients without these antibodies (P < 0.05). CONCLUSIONS: Antibodies against endothelial cells and cardiolipin are present in a subset of patients with clinical and angiographic diagnosis of severe premature atherosclerotic peripheral vascular disease. The lower occurrence of hyperlipidaemia/dyslipidaemia in patients with autoantibodies, in comparison to patients without the antibodies, suggests that these antibodies have a role in vascular damage.

Adult↗
PubMed1995

Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL.

Oxidative modification of LDL has been proposed as an early and crucial step in the development of atherosclerosis, and antibodies against such modified LDL are found in both healthy individuals and patients with atherosclerosis. In this study, 62 patients who were surgically treated for peripheral arterial occlusive disease below the age of 50 were investigated and compared with age- and sex-matched healthy individuals in a case-control study. Autoantibodies against oxidized LDL were measured with an enzyme-linked immunosorbent assay method. Risk factors such as smoking, hypertension, family history of premature cardiovascular events, and lipoprotein levels were also determined. The patients had significantly higher levels of autoantibodies against oxidized LDL; significantly higher levels of total cholesterol, LDL cholesterol, triglycerides, and apo A-I; and significantly lower levels of HDL cholesterol than did control subjects. In multivariate analyses autoantibodies against oxidized LDL discriminated better between patients and control subjects than did any of the different lipoprotein analyses. Among patients, the presence of hypertension and a family history of cardiovascular events were the only factors significantly associated with increased levels of autoantibodies against oxidized LDL.

Adult↗