PubMed Health⌕ Search

Biomedical subjects

S Cederholm-Williams

Publications and source records attributed to S Cederholm-Williams.

9 recordsLinked to original sources
PubMed1999

A model of in vivo human venous thrombosis that confirms changes in the release of specific soluble cell adhesion molecules in experimental venous thrombogenesis.

PURPOSE: The mechanisms of venous thrombogenesis have been studied by using animal models and cells in culture. The results from these systems may not, however, be relevant to the human condition. The aim of this study was to develop a method by which thrombus could be safely produced in a human vein in vivo. The model that was developed was used as a means of studying the changes in soluble adhesion molecule expression in human venous thrombogenesis. METHODS: An autologous thrombin extract was used to generate experimental thrombi in the disconnected portion of the long saphenous veins of 30 patients who were undergoing routine bilateral varicose vein surgery. The contralateral vein was perfused with thrombin extract diluent buffer to act as the control. The concentration of soluble P-, E- and L-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule-1 were measured by means of specific enzyme-linked immunosorbent assays in samples of blood taken from veins in which thrombus had formed and in contralateral control veins. RESULTS: Thrombosis invariably formed when at least 100 IU of thrombin activity was administered. Thrombus formation was independent of the time that the thrombin extract was allowed to remain within the emptied vessel. Thrombosis never developed in control vessels that were similarly treated with the buffer used to dilute the thrombin extract. Experimental thrombi were composed mainly of red cells, with layers of fibrin next to platelet and leukocyte packages. These findings are similar to those observed in samples of established human venous thrombi. There were small but significantly higher levels of the adhesion molecules, soluble P-selectin, and vascular cell adhesion molecule-1 in blood taken from veins in which experimental thrombi had formed, compared with controls (P =.015 and.007, respectively; Wilcoxon signed rank test). Serum levels of soluble L-selectin, E-selectin, and ICAM-1 were not affected by thrombosis. CONCLUSION: This model is safe and reproducible. It produces thrombi with a morphology similar to that described for established human deep venous thrombi. The model may be appropriate for the study of the early changes that occur during human venous thrombogenesis and may also be of value in testing the efficacy of novel antithrombotic agents.

Cell Adhesion Molecules↗
PubMed1995

Cigarette smoking, tar yields, and non-fatal myocardial infarction: 14,000 cases and 32,000 controls in the United Kingdom. The International Studies of Infarct Survival (ISIS) Collaborators.

OBJECTIVES: To assess the effects of cigarette smoking on the incidence of non-fatal myocardial infarction, and to compare tar in different types of manufactured cigarettes. METHODS: In the early 1990s responses to a postal questionnaire were obtained from 13,926 survivors of myocardial infarction (cases) recently discharged from hospitals in the United Kingdom and 32,389 of their relatives (controls). Blood had been obtained from cases soon after admission for the index myocardial infarction and was also sought from the controls. 4923 cases and 6880 controls were current smokers of manufactured cigarettes with known tar yields. Almost all tar yields were 7-9 or 12-15 mg/cigarette (mean 7.5 mg for low tar (< 10 mg) and 13.3 for medium tar (> or = 10 mg). The cited risk ratios were standardised for age and sex and compared myocardial infarction rates in current cigarette smokers with those in non-smokers who had not smoked cigarettes regularly in the past 10 years. RESULTS: At ages 30-49 the rates of myocardial infarction in smokers were about five times those in non-smokers (as defined); at ages 50-59 they were three times those in non-smokers, and even at ages 60-79 they were twice as great as in non-smokers (risk ratio 6.3, 4.7, 3.1, 2.5, and 1.9 at 30-39, 40-49, 50-59, 60-69, 70-79 respectively; each 2P < 0.00001). After standardisation for age, sex, and amount smoked, the rate of non-fatal myocardial infarction was 10.4% (SD 5.4) higher in medium tar than in low tar cigarette smokers (2P = 0.06). This percentage was not significantly greater at ages 30-59 (16.6% (7.1)) than at 60-79 (1.0% (8.5)). In both age ranges the difference in risk between cigarette smokers and non-smokers was much larger than the difference between one type of cigarette and another (risk ratio 3.39 and 3.95 at ages 30-59 for smokers of similar numbers of low and of medium tar cigarettes, and risk ratio 2.35 and 2.37 at ages 60-79). Most possible confounding factors that could be tested for were similar in low and medium tar users, with no significant differences in blood lipid or albumin concentrations. CONCLUSION: The present study indicates that the imminent change of tar yields in the European Union to comply with an upper limit of 12 mg/cigarette will not increase (and may somewhat decrease) the incidence of myocardial infarction, unless they indirectly help perpetuate tobacco use. Even low tar cigarettes still greatly increase rates of myocardial infarction, however, especially among people in their 30s, 40s, and 50s, and far more risk is avoided by not smoking than by changing from one type of cigarette to another.

Adult↗
PubMed1993

An immunohistochemical study of the distribution of plasminogen and plasminogen activators in bullous pemphigoid.

Abnormalities of the cutaneous plasminogen/plasminogen activator system have been associated with acantholytic disorders, psoriasis, keratinocytes in culture, and epidermis in healing wounds. The present study was undertaken to investigate the possible role of the plasmin/plasminogen protease system in lesion development in bullous pemphigoid (BP). Using polyclonal antibodies and a fluorescent technique, the immunohistochemical distribution of plasmin/plasminogen, fibrinogen and the plasminogen activators, urokinase (uPA) and tissue plasminogen activator (tPA), were studied in lesional and non-lesional skin from nine BP patients, one with linear IgA disease (LAD) and one with pemphigoid gestationis (PG). The distribution of the proteases was compared with that in normal skin (n = 4) and in suction blisters (n = 2). In normal skin, fibrinogen, tPA and uPA were absent from the epidermis and plasminogen was confined to the basal layer. Uninvolved BP skin was identical to controls. Focal areas of suprabasal plasminogen expression in the region of a blister was seen in 3/9 BP lesions and in 1/2 suction blisters. In 6/9 BP lesions and both uninvolved and lesional LAD and PG skin were identical to controls, and no suprabasal expression of plasminogen was present. These findings suggest that suprabasal plasminogen expression is unlikely to play a fundamental role in the pathogenesis of blister formation in BP as enhanced expression was not present in every case and the finding was not specific to BP, also occurring in a suction blister. Enhanced plasminogen expression rather may be a reflection of the processes of tissue repair.

Humans↗
PubMed1993

Fibrin cuff lysis in chronic venous ulcers treated with a hydrocolloid dressing.

BACKGROUND: Pericapillary fibrin cuffs (PFC) are a recognized part of the pathology of venous stasis ulcers. A hydrocolloid dressing capable of lysing wound surface fibrin was tested in venous ulcers for its capacity to lyse pericapillary fibrin below the wound surface. METHODS: Tissue biopsies from the rims of 19 venous ulcers were evaluated for thickness of shallow and deep dermal PFCs before and after treatment with DuoDERM covered by Unna's boot and a compression bandage (DD+UB; n = 9) versus the same treatment without the hydrocolloid dressing (UB; n = 10). Frozen sections of all biopsies were stained with an immunofluorescent antibody to fibrin for rating of PFC thickness. Separate sections were stained with hematoxylin and eosin to assess capillary frequency, histopathology, and inflammation. All ratings and pathology assessments were performed blinded to treatment conditions. RESULTS: Both deep and shallow PFCs were reduced in 89% of ulcers treated with DD+UB versus 40% of ulcers treated with UB (alpha < 0.04). No other significant differences in inflammation, histopathology, or capillary frequency were observed. CONCLUSIONS: Treatment with DD+UB reduced PCFs in twice the number of ulcers than UB alone in 1 week. This is the first scientific documentation that a topical wound dressing could reduce the pathophysiology associated with venous ulcers, beyond the known beneficial effect of graduated compression. Not all hydrocolloid dressing are fibrinolytic, so this effect may not generalize to other dressings.

Bandages↗
PubMed1984

Hypercoagulability and coronary artery disease.

Variables of haemostatis were studied in 21 men, aged less than 50 years, with confirmed coronary artery disease but without severe hyperlipidaemia and in 21 healthy controls. Fibrinogen concentrations were significantly raised in the patients, 10 (48%) of whom also showed defective fibrinolysis in response to a standard stress test. These findings suggest that hypercoagulability may be important in the aetiology of some cases of early onset coronary artery disease.

Adult↗
PubMed1978

Whole blood storage in citrate and phosphate solutions containing half-strength trisodium citrate: cellular and biochemical studies.

The efficacy of whole blood preservation in acid citrate dextrose (ACD-A) and citrate-phosphate dextrose (CPD) anticoagulants containing half-strength trisodium citrate concentrations, was determined by biochemical and cellular assessment during 28 day storage at 4 degrees--6 degrees. Erythrocyte 2,3-DPG and ATP concentrations, serum potassium, plasma haemoglobin, and blood pH values were similar between the standard and half-strength citrate counterpart in both ACD-A and CPD series, throughout the entire storage period. Erythrocyte indices (MCV, MCH, MCHC, and osmotic fragility) and the red cell, platelet, and leucocyte counts, were also similar regardless of the final citrate concentration in both ACD-A and CPD series during the 28 day storage period. Tests of coagulation (PT, KCCT, TT, and ethanol gel) and fibrinogen levels were also similar, except for a lower quantity of clottable fibrinogen at day 28 in half-strength CPD. The formation of platelet and leucocyte aggregates during storage, as measured by changes in the SFP, were similar in magnitude whether or not the half-strength citrate formulation was used in ACD-A or CPD. Phagocytic and bactericidal capacity against Staph. aureus was normal following 24-hr storage at 4 degrees--6 degrees, in both ACD-A and CPD preserved blood, regardless of the final citrate concentration. It may now be concluded from this evaluation and those of others, that a reasonable argument can be made for reducing the citrate quantity presently used during blood storage, in order to provide a safe and effective transfusion product for routine use.

Adenosine Triphosphate↗
PubMedDate not supplied

[PC-12 cells hydrolyze the fibrin clot by producing both plasminogen and its tissue activator].

It has been shown that rat pheochromocytoma PC-12 cells degraded fibrin clots in vitro. SDS-PAGE performed in the gels of different density and Western blotting using monoclonal antibodies against DD- and D-fibrin fragments demonstrated that both high and low molecular weight degradation products similar to those of fibrin hydrolysis by plasmin had been formed. Enzyme electrophoresis, chromogenic assay and enzyme-linked immunosorbent assay using tPA-specific antibodies demonstrated that PC-12 cells constitutively secreted both plasminogen and tPA. The results obtained allow using PC-12 cells as a model to examine the interaction of nerve cells with the fibrin clot.

Animals↗
PubMedDate not supplied

[The role of fibrin clot degradation products in the regulation of vital functions of PC-12 cells].

The products of the fibrin clot hydrolysis performed by PC-12 cells modulated dose-dependently the rate of cell proliferation and favored their survival when seeded in suboptimal density. Co-incubation of PC-12 cells with fibrin degradation products enhanced cell adhesion to tissue culture plastic, as well as the number of nicotinic acetylcholine receptor alpha3 and alpha5 subunits expressed. It was demonstrated that, in fact, such a heterogeneous and comprehensive influence was a sum of effects exerted by different fibrin fragments. Low molecular weight fraction (below 30 kDa), but not a purified alphaC-domain, stimulated PC-12 cell proliferation, diminished their adhesion to plastic, increased nicotinic receptor expression and caused processes outgrowth. On the contrary, high molecular weight products, in particular D, DD and E fragments, enhanced PC-12 adhesion to plastic and, as a result, slowed cell division. Both high and low molecular weight fragments favored the survival of PC-12 cells. These results showed that fibrin degradation products support the vital functions of neuron-like cells, favor their contacts with extracellular surrounding and act as neurotrophic factors.

Animals↗