32 results on '"Ludlam CA"'
Search Results
2. Microparticles, malignancy and thrombosis.
- Author
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Zahra S, Anderson JA, Stirling D, and Ludlam CA
- Subjects
- Cell-Derived Microparticles immunology, Female, Humans, Immunophenotyping, Male, Neoplasms complications, Thrombosis etiology, Thrombosis immunology, Cell-Derived Microparticles physiology, Neoplasms physiopathology, Thrombosis physiopathology
- Abstract
Microparticles (MPs) are considered to be important biological effectors of several different physiological and pathological processes. There is increasing evidence of their role in haemostasis and thrombosis, and also of their importance in cancer cell survival, invasiveness and metastasis. The level of circulating MPs has been assessed in many different disease states, and there are reports that patients with malignancy and patients with thrombosis have increased levels of circulating MPs and MP-dependent thrombogenic potential. Research into the function and effect of MPs is currently hampered by a lack of standardization in the methods used to identify and quantify them. As these methods improve it is likely that MP assays will be of use both diagnostically and therapeutically in the future., (© 2011 Blackwell Publishing Ltd.)
- Published
- 2011
- Full Text
- View/download PDF
3. Guideline for investigation and management of adults and children presenting with a thrombocytosis.
- Author
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Harrison CN, Bareford D, Butt N, Campbell P, Conneally E, Drummond M, Erber W, Everington T, Green AR, Hall GW, Hunt BJ, Ludlam CA, Murrin R, Nelson-Piercy C, Radia DH, Reilly JT, Van der Walt J, Wilkins B, and McMullin MF
- Subjects
- Adult, Algorithms, Child, Diagnosis, Differential, Evidence-Based Medicine methods, Humans, Myelodysplastic Syndromes diagnosis, Myelodysplastic-Myeloproliferative Diseases diagnosis, Myeloproliferative Disorders diagnosis, Risk Assessment methods, Thrombocythemia, Essential diagnosis, Thrombocythemia, Essential therapy, Thrombocytosis etiology, Thrombocytosis therapy, Thrombocytosis diagnosis
- Published
- 2010
- Full Text
- View/download PDF
4. An update on the assessment and management of the risk of transmission of variant Creutzfeldt-Jakob disease by blood and plasma products.
- Author
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Turner ML and Ludlam CA
- Subjects
- Animals, Blood Component Transfusion adverse effects, Consumer Product Safety, Creutzfeldt-Jakob Syndrome prevention & control, Humans, PrPSc Proteins analysis, Risk Assessment methods, Risk Management methods, Creutzfeldt-Jakob Syndrome transmission, Public Health, Transfusion Reaction
- Abstract
There have been four highly probable instances of variant Creutzfeldt-Jakob disease (vCJD) transmission by non-leucocyte depleted red cell concentrates and it is now clear that the infectious agent is transmissible by blood components. To date there in no reported evidence that the infectious agent has been transmitted by fractionated plasma products, e.g. factor VIII concentrate. This review outlines current and potential risk management strategies including donor deferral criteria, the potential for donor screening, blood component processing and prion reduction filters, plasma product manufacture and the difficulties in identification and notification of those considered 'at risk of vCJD for public health purposes'.
- Published
- 2009
- Full Text
- View/download PDF
5. Plasma microparticles and vascular disorders.
- Author
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Lynch SF and Ludlam CA
- Subjects
- Blood Coagulation Factors metabolism, Endothelium, Vascular pathology, Humans, Leukocytes pathology, Phospholipids metabolism, Plasma, Platelet Activation, Signal Transduction physiology, Vascular Diseases pathology, Vascular Diseases blood
- Abstract
Microparticles are circulating, phospholipid rich, submicron particles released from the membranes of endothelial cells, platelets, leucocytes and erythrocytes. Investigation into their biological activity has revealed diverse actions in coagulation, cell signalling and cellular interactions. These actions are mediated through their phospholipid rich surfaces and the expression of cell surface molecules which reflect their cell of origin and its state of activation. Microparticle numbers are reported to be elevated in a number of conditions where vascular dysfunction and inflammation are important pathophysiological mechanisms, for example coronary artery disease or thrombotic microangiopathies. Currently, there are a variety of different methods used for the quantitation of circulating microparticles; however with standardisation their assessment may prove to be of clinical value, reflecting the state of the vasculature. Knowledge of the functional properties of microparticles will contribute to our understanding of the mechanisms underlying vascular dysfunction and prothrombotic states.
- Published
- 2007
- Full Text
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6. Managing the risk of transmission of variant Creutzfeldt Jakob disease by blood products.
- Author
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Ludlam CA and Turner ML
- Subjects
- Animals, Blood microbiology, Blood Donors, Blood Transfusion methods, Creutzfeldt-Jakob Syndrome prevention & control, Disease Transmission, Infectious prevention & control, Humans, Prion Diseases transmission, Creutzfeldt-Jakob Syndrome transmission, Transfusion Reaction
- Abstract
Whereas plasma-derived clotting factor concentrates now have a very good safety record for not being infectious for lipid enveloped viruses, concern has arisen about the possibility that prion diseases might be transmitted by blood products. There is epidemiological evidence that classical sporadic Creutzfeld Jakob disease (CJD) is not transmitted by blood transfusion. There is now good evidence that the abnormal prion associated with variant CJD can be transmitted by transfusion of fresh blood components and infect recipients. To reduce the risk of the pathological prion in the UK infecting recipients of clotting factor concentrates, these are now only manufactured from imported plasma collected from countries where there has not been bovine spongiform encephalopathy (BSE) in cattle and the risk of variant CJD in the population is, therefore, considered negligible. The safety of these concentrates is also enhanced because prion protein is, to an appreciable extent, excluded by the manufacturing process from the final product. To help reduce the chance of prion transmission by fresh blood products, donations are leucodepleted, there is increasing use of imported fresh frozen plasma (especially for treating children) and potential donors, who have been recipients of blood since 1980 (the beginning of the BSE epidemic in cattle) are deferred.
- Published
- 2006
- Full Text
- View/download PDF
7. A prospective study of recombinant activated factor VII administered by continuous infusion to inhibitor patients undergoing elective major orthopaedic surgery: a pharmacokinetic and efficacy evaluation.
- Author
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Ludlam CA, Smith MP, Morfini M, Gringeri A, Santagostino E, and Savidge GF
- Subjects
- Adult, Amputation, Surgical, Antigens blood, Arthroplasty, Replacement, Knee, Blood Loss, Surgical, Factor VII pharmacokinetics, Factor VIIa, Female, Hemostasis, Surgical methods, Hemostatics pharmacokinetics, Humans, Infusions, Intravenous, Male, Middle Aged, Postoperative Hemorrhage prevention & control, Prospective Studies, Recombinant Proteins pharmacokinetics, Treatment Outcome, Factor VII administration & dosage, Hemophilia A complications, Hemostatics administration & dosage, Recombinant Proteins administration & dosage
- Abstract
After surgery in haemophilia, haemostasis is difficult to maintain in the presence of an antifactor VIII antibody. This study assessed the pharmacokinetics of recombinant activated factor VII (rFVIIa) and its efficacy in securing post-operative haemostasis in haemophiliacs with inhibitors. Continuous infusion of rFVIIa was evaluated for elective major orthopaedic surgery in nine patients with neutralizing antibodies to FVIII and at high risk of bleeding. After an initial preoperative bolus of 90 micro g/kg, rFVIIa was infused at a fixed rate of 50 micro g/kg/h for a median of 20 d (range 7-20 d). The median plasma FVII coagulant activity (FVII:C) at 24 h, 72 h and 20 d after surgery was 38 IU/ml (range 22-169 IU/ml), 45 IU/ml (range 17-88 IU/ml) and 31 IU/ml (range 27-46 IU/ml) respectively. The median plasma FVIIa:C at the same time points was 51 (range 24-211), 63 (range 22-99) and 44 (range 28-76) IU/ml respectively. Median total rFVIIa clearance remained stable during the rFVIIa continuous infusion period and was 40 (range 9-70), 34 (range 17-86) and 48 (range 32-55)ml/kg/h at the end of 24 h, 72 h and 20 d infusion respectively. Post-operatively, there were bleeds in six patients, which settled readily after a single bolus of rFVIIa (60 micro g/kg). There was a good clinical outcome for all patients. These data indicate that rFVIIa infusion at 50 micro g/kg/h achieves continuous plasma FVII procoagulant activity in excess of 30 IU/ml (12-15 nmol/l) and provides adequate haemostatic control for inhibitor patients during major orthopaedic surgery.
- Published
- 2003
- Full Text
- View/download PDF
8. The successful use of plasma exchange and immunosuppression in the management of acquired Glanzmann's thrombasthenia.
- Author
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Thomas RV, Bessos H, Turner ML, Horn EH, and Ludlam CA
- Subjects
- Anticoagulants adverse effects, Combined Modality Therapy, Female, Gastrointestinal Hemorrhage drug therapy, Gastrointestinal Hemorrhage etiology, Heparin adverse effects, Hirudin Therapy methods, Humans, Iliac Vein, Middle Aged, Thrombocytopenia chemically induced, Venous Thrombosis chemically induced, Venous Thrombosis drug therapy, Azathioprine therapeutic use, Immunosuppressive Agents therapeutic use, Plasma Exchange methods, Thrombasthenia therapy
- Published
- 2002
- Full Text
- View/download PDF
9. Interleukin 6 and haemostasis.
- Author
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Kerr R, Stirling D, and Ludlam CA
- Subjects
- Arteriosclerosis therapy, Blood Platelets physiology, Endothelium, Vascular metabolism, Factor VIII metabolism, Fibrinogen metabolism, Hepatocytes metabolism, Humans, Interleukin-6 therapeutic use, Leukocytes metabolism, Models, Biological, Receptors, Interleukin-6 metabolism, Thromboplastin metabolism, Venous Thrombosis blood, Venous Thrombosis therapy, von Willebrand Factor metabolism, Blood Coagulation Factors metabolism, Hemostasis physiology, Interleukin-6 physiology, Thrombosis blood
- Published
- 2001
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10. The management of 'low-risk' and 'intermediate-risk' patients with primary thrombocythaemia. MPD (UK) Study Group.
- Author
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Pearson TC, Bareford D, Craig J, Egan EL, Green AR, Lucas GS, Ludlam CA, McMullin MF, Messinezy M, Oscier DG, and Reilly JT
- Subjects
- Adolescent, Adult, Aged, Humans, Middle Aged, Risk Factors, Thrombocytosis therapy
- Published
- 1999
- Full Text
- View/download PDF
11. TGF-beta is not the principal immunosuppressive component in coagulation factor concentrates.
- Author
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Pearson HJ, Stirling D, Ludlam CA, and Steel CM
- Subjects
- Animals, Cell Division, Cells, Cultured, Humans, Lymphocytes cytology, Mice, Blood Coagulation Factors immunology, Immune Tolerance immunology, Transforming Growth Factor beta immunology
- Abstract
Coagulation factor concentrates are known to inhibit a variety of immune reactions when assessed in vitro. This study assessed the immunomodulatory activity of a wide range of coagulation factor concentrates by measuring their inhibition of PHA-stimulated lymphocyte proliferation and reduction in IL-2 secretion. The hypothesis that TGF-beta is responsible for most of these effects was tested by measuring biologically active TGF-beta and immunoreactive TGF-beta1 in the concentrates and comparing the levels recorded with immunosuppressive activity. In addition, the coagulation factors were compared directly with a standard preparation of TGF-beta in a TGF-beta-specific bioassay and in lymphocyte proliferation assays. Although there was a broad correlation between levels of total or active TGF-beta and immunosuppressive activity across all of the coagulation factors tested, individual data sets showed clear discrepancies. Implying that TGF-beta probably serves as a surrogate marker for other immunomodulatory contaminants and that neither TGF-beta nor any other single substance could account for all of the immunosuppressive activity observed. Furthermore, there was a difference of more than 100-fold in the relative potencies of coagulation factors and pure TGF-beta, when compared in immunosuppression assays, indicating that the different assays did not measure the same substance. Whereas anti-TGF-beta antibody almost completely blocked the activity of coagulation factor concentrates (TGF-beta-specific bioassay) and abrogated the effect of authentic TGF-beta (immunosuppression assays) at high concentrations it achieved <50% reversal of the immunosuppressive effects of coagulation factors in immunosuppression assays. These findings indicated that TGF-beta accounted for only a minor proportion of the immunosuppressive activity in most coagulation factor concentrates.
- Published
- 1999
- Full Text
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12. Is albumin harmful?
- Author
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Drummond GB and Ludlam CA
- Subjects
- Disease Transmission, Infectious, Humans, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Albumins adverse effects
- Published
- 1999
- Full Text
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13. The effect of monoclonal or ion-exchange purified factor VIII concentrate on HIV disease progression: a prospective cohort comparison.
- Author
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Hay CR, Ludlam CA, Lowe GD, Mayne EE, Lee RJ, Prescott RJ, and Lee CA
- Subjects
- CD4 Lymphocyte Count, Cohort Studies, Disease Progression, Hemophilia A complications, Humans, Ion Exchange, Prospective Studies, Survival Analysis, Survival Rate, Blood Component Transfusion methods, Factor VIII administration & dosage, HIV Infections complications, Hemophilia A therapy
- Abstract
The CD4 count has been reported to decline less rapidly in HIV-infected haemophiliacs treated with monoclonally purified factor VIII concentrates than in those using intermediate-purity concentrates. No survival advantage has been demonstrated for this effect, and it is unclear whether this effect occurs with all high-purity concentrates. Two cohorts of patients with severe haemophilia A and HIV treated with either ion-exchange-purified or monoclonally-purified concentrates were compared. The CD4 count, survival, AIDS-defining illnesses, CDC category and anti-retroviral therapy were recorded at 6-monthly intervals for 3 years following the change from intermediate to high-purity factor VIII. 116 patients were recruited, 37 of whom were treated with an ion-exchange purified factor VIII concentrate at three centres, mean (SD) age 31.1 (12.2) years, and 79 were treated with monoclonally purified factor VIII concentrate at two centres, mean (SD) age 29.8 (11.2) years. At the start of the study the median CD4 count was (monoclonal v ion-exchange) 0.30 v 0.16 x 10(9)/l. The CD4 count declined in both arms to a median of (monoclonal v ion-exchange) 0.16 v 0.08 x 10(9)/l at the final visit. Analysis of the (CD4 count)(1/2) over time, using a random coefficients model, found that the mean (SE) rates of decline were not statistically significantly different in the two treatment groups (monoclonal v ion exchange: -0.050 (0.008) v -0.034 (0.011) (CD4 count)(1/2) per year, P = 0.24). No statistically significant difference in survival (log-rank test: P = 0.33) was found. There was no difference in the proportion of individuals experiencing one or more AIDS-defining illnesses (P = 0.32) or in the proportion progressing to CDC category IV (P = 0.28) during the study. The CD4 count declined during the study at a rate similar to that previously reported in patients treated with intermediate-purity factor VIII concentrate, and there was no evidence of any difference between the two treatment groups.
- Published
- 1998
- Full Text
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14. Liver biopsy in haemophilia.
- Author
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Ludlam CA, Hanley JP, and Hayes PC
- Subjects
- Hemorrhage etiology, Humans, Biopsy adverse effects, Hemophilia A complications
- Published
- 1997
15. Development of anti-interferon antibodies and breakthrough hepatitis during treatment for HCV infection in haemophiliacs.
- Author
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Hanley JP, Jarvis LM, Simmonds P, and Ludlam CA
- Subjects
- Adolescent, Adult, Aged, Female, Hepatitis C immunology, Humans, Interferon alpha-2, Interferon-alpha therapeutic use, Male, Middle Aged, Recombinant Proteins, Antibodies immunology, Hemophilia A complications, Hepatitis C therapy, Interferon-alpha immunology
- Abstract
The development of anti-interferon antibodies may lead to treatment failure during interferon therapy. We have studied the development of such antibodies in a group of 39 haemophiliacs receiving interferon-alpha 2a for chronic hepatitis C virus (HCV) infection. Anti-interferon antibodies developed in five (13%) patients and were associated with "breakthrough hepatitis' in three cases. There was an association between the development of anti-interferon antibodies and infection with HCV genotype 3a (P = 0.01). This study suggests that the development of anti-interferon antibodies may lead to treatment failure in a proportion of haemophiliacs with HCV infection. The association with genotype 3a has not previously been reported. Monitoring for the development of breakthrough hepatitis due to anti-interferon antibodies may provide the opportunity to develop strategies to overcome their effects.
- Published
- 1996
- Full Text
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16. Investigation of chronic hepatitis C infection in individuals with haemophilia: assessment of invasive and non-invasive methods.
- Author
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Hanley JP, Jarvis LM, Andrews J, Dennis R, Lee R, Simmonds P, Piris J, Hayes P, and Ludlam CA
- Subjects
- Adolescent, Adult, Aged, Biopsy methods, Child, Chronic Disease, Cohort Studies, Endoscopy, Evaluation Studies as Topic, Female, Genotype, HIV Infections complications, Hepatitis C diagnosis, Humans, Laparotomy, Male, Middle Aged, Predictive Value of Tests, Ultrasonography, Hemophilia A complications, Hepatitis C complications
- Abstract
Hepatitis C virus (HCV) infection is the major cause of chronic liver disease in individuals with haemophilia. A wide spectrum of disease severity is found in this group, ranging from mild hepatitis to cirrhosis. We have studied a cohort of 87 anti-HCV positive haemophiliacs who have been infected with HCV for 10-25 years and assessed the relative value of invasive and non-invasive methods of evaluating liver disease. The severity of liver disease was assessed using ultrasound scan (n = 77), upper GI endoscopy (n = 50), laparoscopic liver inspection (n = 33) and liver biopsy (n = 22). Invasive investigations were performed without any significant bleeding complications. Evidence of severe liver disease was found in approximately 25% of patients. There was agreement between the severity of liver histology and the information derived from the laparoscopic liver inspection, endoscopy and ultrasound in 86%. Co-infection with HIV was significantly associated with more severe liver disease (P = 0.006). This study provides further evidence that liver disease is emerging as a major complication in haemophiliacs and severe liver disease is more common in those co-infected with HIV. We have shown the potential value of laparoscopic liver inspection, in combination with endoscopy and ultrasound, in staging the extent of liver disease, and suggest that most patients may be managed without resorting to liver biopsy.
- Published
- 1996
- Full Text
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17. Low proteins C and S and activation of fibrinolysis in treated essential thrombocythemia.
- Author
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Wieczorek I, MacGregor IR, and Ludlam CA
- Subjects
- Adult, Aged, Female, Fibrinolysis, Humans, Male, Middle Aged, Veins pathology, Protein C analysis, Protein S analysis, Thrombocytosis blood
- Abstract
The aim of this study was to investigate whether abnormalities in the fibrinolytic system and in the naturally occurring anticoagulant proteins could contribute to the thrombotic risk in essential thrombocythemia. Euglobulin lysis time, fibrin plate lysis area, tissue plasminogen activator antigen, and activity and plasminogen activator inhibitor antigen were measured before and after venous occlusion in a group of 16 patients with essential thrombocythemia and in 16 healthy age and sex matched controls. In addition, resting levels of antithrombin III, D-dimer, prothrombin fragment 1 + 2, and protein C and S were assessed. The results were related to the presence or absence of a thrombotic history. The results demonstrated that the patients had a significantly elevated fibrin plate lysis area and significantly decreased plasminogen activator antigen, both at baseline and after venous occlusion. They also had significantly decreased levels of plasma protein C and total protein S. There was a modest, non-significant elevation in the plasma concentration of D-Dimer and F 1 + 2. Those patients with a history of thrombosis had significantly lower protein C levels compared with individuals without a thrombotic history. We conclude that patients with essential thrombocythemia have evidence of activated fibrinolysis in the resting state and after stimulation. This, and the decreased levels of protein C and total protein S, may be secondary to chronic clinically occult thrombosis occurring in myeloproliferative disorders.
- Published
- 1995
- Full Text
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18. Acquired haemophilia and its management.
- Author
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Morrison AE and Ludlam CA
- Subjects
- Hemophilia A diagnosis, Hemophilia A etiology, Hemorrhage therapy, Humans, Immunotherapy, Hemophilia A therapy
- Published
- 1995
- Full Text
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19. Absence of hepatitis A virus transmission by high-purity solvent detergent treated coagulation factor concentrates in Scottish haemophiliacs.
- Author
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Watson HG, Ludlam CA, McOmish F, Dennis R, Hart H, and Simmonds P
- Subjects
- Adolescent, Adult, Base Sequence, Child, Factor VIII isolation & purification, Hemophilia A drug therapy, Hepatitis A complications, Hepatitis A Virus, Human isolation & purification, Humans, Male, Molecular Sequence Data, Organophosphates, Polymerase Chain Reaction, Polysorbates, Retrospective Studies, Drug Contamination, Factor VIII therapeutic use, Hemophilia A complications, Hepatitis A transmission
- Abstract
Recent reports of hepatitis A virus (HAV) infection in haemophiliacs receiving high-purity solvent detergent (HP.SD) treated factor VIII concentrates have brought into question the efficacy of this virucidal method for inactivating HAV. To assess whether HAV may have been transmitted by HP.SD concentrates, we compared seroprevalence in haemophiliacs with different disease severity, sought evidence of seroconversion to HAV since introduction of HP.SD products, and directly examined concentrates for HAV RNA by PCR. Our data suggest that Scottish haemophiliacs are not being infected with HAV by HP.SD concentrates produced initially by CRTS Lille and presently by PFC Edinburgh and supplied by the Scottish National Blood Transfusion Service (SNBTS).
- Published
- 1995
- Full Text
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20. Enhancement of human T cell responses to allogeneic stimuli by factor VIII concentrates.
- Author
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Batchelor A, Steel CM, and Ludlam CA
- Subjects
- Cell Division immunology, Cells, Cultured, Factor IX immunology, Factor VIII isolation & purification, Hemophilia A immunology, Humans, Lymphocyte Culture Test, Mixed, Male, Factor VIII immunology, T-Lymphocytes immunology
- Abstract
The effect of factor VIII concentrate, from commercial and National Health Services manufacturers, on in vitro lymphocyte proliferative response to allogeneic stimulator cells was investigated. Factor VIII preparations 'purified' by ion exchange or by monoclonal antibody affinity had no effect in this assay but lymphocyte proliferation in response to allogeneic cells was markedly and consistently enhanced by some intermediate purity factor VIII concentrates and, to a lesser extent, by a factor IX preparation. These preparations did not stimulate lymphocyte proliferation in the absence of other mitogens. The co-mitogenic factor(s) present in intermediate purity factor VIII was not identified. However, enhanced proliferation was not due to factor VIII itself, nor to albumin or fibronectin. The clinical relevance of the immunomodulatory activity of intermediate purity factor VIII concentrates in vitro is discussed.
- Published
- 1992
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21. Use of several second generation serological assays to determine the true prevalence of hepatitis C virus infection in haemophiliacs treated with non-virus inactivated factor VIII and IX concentrates.
- Author
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Watson HG, Ludlam CA, Rebus S, Zhang LQ, Peutherer JF, and Simmonds P
- Subjects
- Drug Contamination, Hemophilia A drug therapy, Hemophilia B drug therapy, Hepatitis C complications, Hepatitis C transmission, Humans, Male, Prevalence, Scotland epidemiology, Factor IX therapeutic use, Factor VIII therapeutic use, Hemophilia A complications, Hemophilia B complications, Hepatitis C epidemiology
- Abstract
To investigate the prevalence of hepatitis C virus infection in two risk groups, stored serum samples from treated haemophiliacs and intravenous drug users were tested for anti-HCV by both anti-C-100 based and second generation ELISAs (Abbott and Ortho) followed by testing in two confirmatory immunoblot assays that incorporate core as well as other non-structural antigens (Innogenetics LIA and Chiron RIBA-HCV test). Clear evidence of HCV infection was found in all but one of 78 haemophiliacs treated with non-virus inactivated clotting factor concentrates, but in none exposed only to super dry heat-treated concentrates. Only four samples gave rise to conflicting serological results between the four tests, two of these occurred in patients with advanced HIV related disease and almost certainly reflected loss of humoral immunity associated with disease progression, and the others occurred in the only two patients tested who were chronic carriers of hepatitis B infection and may reflect an interaction between the two viruses. Comparison of anti-C-100 versus second generation tests in immunocompetent drug users revealed a false negative rate of 20% using C-100 alone, indicating the advantage of using second generation assays for detection of past or current HCV infection. Of all of the antigens used in the confirmatory assay, positive sera showed strongest and most frequent reactivity with the C22 and C33c proteins (Ortho RIBA).
- Published
- 1992
- Full Text
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22. Immunological studies in HIV seronegative haemophiliacs: relationships to blood product therapy.
- Author
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Cuthbert RJ, Ludlam CA, Steel CM, Beatson D, and Peutherer JF
- Subjects
- Humans, Immunity, Cellular, Immunoglobulins analysis, Intradermal Tests, Leukocyte Count, Lymphocyte Activation, Lymphocyte Subsets, T-Lymphocyte Subsets, Factor IX therapeutic use, Factor VIII therapeutic use, HIV Seropositivity immunology, Hemophilia A immunology, Hemophilia B immunology
- Abstract
Immunological studies were performed on a group of 44 haemophilia A and 15 haemophilia B patients who were treated exclusively with blood products manufactured by the Scottish National Blood Transfusion Service (SNBTS). All patients were HIV seronegative throughout the study. Of the haemophilia A patients 14 (32%) had CD4+ lymphocyte subset counts less than or equal to 0.5 x 10(9)/l, compared with one (6%) haemophilia B patient and four (8%) controls. The percentage of activated T cells was greater than 5% in 19/33 (57%) with haemophilia A, 5/9 (55%) haemophilia B and 14/50 (28%) of control subjects. beta 2 microglobulin values greater than or equal to 2.0 mg/l were observed in 19 (43%) haemophilia A and four (26%) haemophilia B patients, compared with one (2%) control. No significant increases in serum interleukin-2 receptor concentrations were observed in 15 haemophilia A and one haemophilia B patients. Significantly elevated levels of IgG, IgM and IgA were observed in the haemophilia A group, but elevation of immunoglobulins was restricted to the IgG class in the haemophilia B group. Of the haemophilia A patients 16/30 (53%) and 6/11 (54%) haemophilia B patients had depression of cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity responses to intradermally injected recall antigens. There was no correlation between factor VIII or factor IX usage and changes in lymphocyte subsets, beta 2 microglobulin, and immunoglobulin levels. There was, however, a strong correlation between annual factor VIII usage and the degree of depression of CMI for those with haemophilia A but not for those with haemophilia B. No correlation between alterations in the immune parameters and disturbance of liver function tests was observed in either haemophilia A or haemophilia B patients. We conclude that alloantigen or non-HIV viral exposure due to repeated administration of factor concentrates brings about alterations in the immune response, and that these changes are more marked following exposure to intermediate purity factor VIII compared with factor IX concentrate.
- Published
- 1992
- Full Text
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23. Carrier detection in haemophilia a by immunological measurement of factor VIII related antigen (VIIIRAg) and factor VIII clotting antigen (VIIICAg).
- Author
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Peake IR, Newcombe RG, Davies BL, Furlong RA, Ludlam CA, and Bloom AL
- Subjects
- Factor VIII analysis, Female, Hemophilia A immunology, Humans, Radioimmunoassay, von Willebrand Factor, Antigens analysis, Factor VIII immunology, Genetic Carrier Screening methods, Hemophilia A genetics
- Abstract
23 obligate carriers of mild and severe haemophilia A and 26 normal females were bled on three occasions, and their plasmas assayed for procoagulant factor VIII (VIIIC), factor VIII related antigen (VIIIRAg) and factor VIII clotting antigen (VIIICAg). A comparison of the ratios VIIIC/VIIIRAg and VIIICAg/VIIIRAg indicated that, although the two ratios gave the same proportional misclassification of carriers as normals (four of 23), the latter ratio showed greater discriminatory power when an unequal variances predictive method was used to calculate likelihood ratios (for carrier status). This greater power was shown to be due to a greater reproducibility between visits for the VIIICAg/VIIIRAg ratio. Discrimination was considerably better when the median of the three median values for each variable was analysed, compared to the median value obtained at the first visit. There was also no statistical difference between VIIICAg/VIIIRAg (or VIIIC/VIIIRAg) ratios obtained from carriers of severe compared to mild haemophilia.
- Published
- 1981
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24. Survival of 111-indium platelet subpopulations of varying density in normal and post splenectomized subjects.
- Author
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Watson HH and Ludlam CA
- Subjects
- Adult, Blood Platelets physiopathology, Cell Survival, Centrifugation, Density Gradient, Humans, Indium, Male, Middle Aged, Oxyquinoline analogs & derivatives, Postoperative Period, Radioisotopes, Splenectomy, Blood Platelets physiology, Hodgkin Disease blood, Organometallic Compounds
- Abstract
The present study was designed to investigate the survival of platelets of differing densities in normal and post-splenectomized subjects. Autologous platelets, labelled with 111In-oxine, were reinjected into normal subjects (n = 12); 63% were recovered in the circulation and their survival curve was linear with a T 1/2 of 4.5 d. When the platelets were layered onto a continuous Percoll gradient, they formed a band extending between 1.040 and 1.080 g ml-1. After fractionation of the gradient the specific radioactivity of 111In platelets recovered was measured. The specific activity of low density platelets (average 1.050 g ml-1) decreased rapidly with a T 1/2 of 2.0 d, whilst medium density platelets (average 1.060 g ml-1) survived with a T 1/2 of 4.5 d; high density platelets (average 1.073 g ml-1) exhibited a T 1/2 greater than 5.0 d. This latter population of high density platelets also showed a significant increase in specific activity on the first day following injection. In post-splenectomy subjects a similar relationship between density and 111In associated activity was observed but no increase in the specific activity of the dense platelets on day 1 was observed. We conclude that high density autologous 111In-platelets are preferentially retained in the spleen and have a more prolonged survival than those of lower density.
- Published
- 1986
- Full Text
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25. Transfusion associated graft-versus-host disease in T-cell chronic lymphocytosis.
- Author
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Sheehan T, McLaren KM, Salter D, and Ludlam CA
- Subjects
- Chronic Disease, Humans, Male, Middle Aged, T-Lymphocytes, Erythrocyte Transfusion, Graft vs Host Disease etiology, Lymphocytosis complications, Transfusion Reaction
- Published
- 1988
- Full Text
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26. An immunoradiometric assay for procoagulant factor VIII antigen: results in haemophilia, von Willebrand's disease and fetal plasma and serum.
- Author
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Peake IR, Bloom AL, Giddings JC, and Ludlam CA
- Subjects
- Antigens analysis, Factor VIII blood, Female, Hemophilia A blood, Humans, Infant, Newborn, Male, Radioimmunoassay, von Willebrand Diseases blood, Factor VIII immunology, Fetal Blood immunology, Hemophilia A immunology, von Willebrand Diseases immunology
- Abstract
An immunoradiometric assay (IRMA) has been developed based on the inhibitor which arose in a polytransfused severe haemophiliac. The two-site IRMA measures antigens closely associated with the procoagulant parts of the factor VIII complex, which are termed FVIIC antigens or FVIIICAG. FVIIICAG was present in normal plasma and also, at a slightly lower concentration, in normal serum. In 37 patients with haemophilia A, 36 had FVIIICAG levels of less than 10% of the normal plasma pool. In patients with von Willebrand's disease the levels of FVIIIC and FVIIICAG were in good agreement, both before and after treatment with cryoprecipitate or DDAVP. FVIIICAG was relatively stable in plasma at 37 degrees C and could also be detected in cord and fetal serum. The assay is of potential value for detecting reduced levels of factor VIII, for carrier detection and for the prenatal diagnosis of haemophilia.
- Published
- 1979
- Full Text
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27. Three approaches to the radioimmunoassay of human beta-thromboglobulin.
- Author
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Bolton AE, Ludlam CA, Moore S, Pepper DS, and Cash JD
- Subjects
- Beta-Globulins metabolism, Humans, Immune Sera analysis, Iodine Radioisotopes, Radioimmunoassay, Beta-Globulins analysis
- Abstract
Three radioimmunoassays for the measurement of beta-thromboglobulin are described. The standard method, using antiserum in solution, could be used to measure plasma concentrations of beta-thromboglobulin with the results available after 2-3 d. The use of a greater dilution of antiserum and tracer, with delayed addition of tracer, resulted in a more sensitive assay suitable for measuring b-thromboglobulin in urine. The use of a solid-couples antiserum under non-equilibrium conditions allowed the measurement of plasma levels of beta-thromboglobulin after an assay incubation time of 1 h. These three radioimmunoassay systems for beta-thromboglobulin cover the likely clinical requirements for the measurement of this platelet specific protein.
- Published
- 1976
- Full Text
- View/download PDF
28. Evidence for the platelet specificity of beta-thromboglobulin and studies on its plasma concentration in healthy individuals.
- Author
-
Ludlam CA
- Subjects
- Adult, Age Factors, Aged, Blood Cell Count, Blood Platelets cytology, Cell Survival, Erythrocytes analysis, Female, Humans, Leukocytes analysis, Male, Middle Aged, Radioimmunoassay, Tissue Distribution, Beta-Globulins analysis, Blood Platelets analysis
- Abstract
The concentration of normal human platelet beta-thromboglobulin (beta-TG) was measured in various washed organ samples by a radioimmunoassay. As only trace amounts were detected, beta-TG appears to be a platelet specific protein. Assay of beta-thromboglobulin in plasma samples from 180 normal individuals gave a range of 10--65 mg/ml. In the 10 subjects studied, plasma beta-TG concentration was related to platelet lifespan but not to turnover. The plasma beta-TG concentration rose with increasing age but did not correlate with the whole blood platelet count or the percentage of megathrombocytes. These results provide further substantial evidence that measurement of plasma beta-TG concentration is useful for assessing the participation of platelets in various disease processes.
- Published
- 1979
- Full Text
- View/download PDF
29. Human immunodeficiency virus detection: correlation with clinical progression in the Edinburgh haemophiliac cohort.
- Author
-
Cuthbert RJ, Ludlam CA, Rebus S, Peutherer JF, Aw DW, Beatson D, Steel CM, and Reynolds B
- Subjects
- Acquired Immunodeficiency Syndrome microbiology, Cohort Studies, HIV Antibodies analysis, HIV Antigens analysis, Humans, Lymphocytes microbiology, Scotland, AIDS Serodiagnosis, Acquired Immunodeficiency Syndrome etiology, Hemophilia A complications
- Abstract
HIV p24 antigenaemia and virus detection in cultures of peripheral blood lymphocytes were examined in 16 of 18 haemophiliacs infected with HIV by a single batch of Scottish National Blood Transfusion Service factor VIII concentrate. Six (38%) had p24 antigenaemia and 11 (69%) had positive lymphocyte cultures. All seven patients with serious HIV disease (CDC group IV) had positive lymphocyte cultures whereas four (57%) had p24 antigenaemia. Four of nine (44%) patients with asymptomatic HIV disease (CDC groups II and III) had positive cultures and two (22%) had p24 antigenaemia. Twenty-eight of 36 samples from the symptomatic group were HIV culture positive compared with nine of 30 samples from the asymptomatic group (P less than 0.001). None of 14 antibody negative haemophiliacs who also received the implicated batch of factor VIII had p24 antigenaemia or positive HIV cultures. The ability to detect HIV in cultured lymphocytes correlates with the clinical severity of HIV disease in this cohort.
- Published
- 1989
- Full Text
- View/download PDF
30. Immunohistological diagnosis of a case of composite lymphoma.
- Author
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Salter DM, Sheehan T, Krajewski AS, and Ludlam CA
- Subjects
- Aged, Antibodies, Monoclonal, B-Lymphocytes pathology, Histiocytes pathology, Humans, Immunoenzyme Techniques, Lymphocytes pathology, Male, Neoplasms, Multiple Primary diagnosis, Hodgkin Disease diagnosis, Leukemia, Lymphocytic, Chronic, B-Cell diagnosis
- Abstract
A case of composite lymphoma consisting of Hodgkin's disease and B cell lymphocytic lymphoma is described. A diagnosis of lymphocyte predominant Hodgkin's disease was made initially by histology. The presence of a composite lymphoma was only appreciated once immunohistochemistry was available. The findings illustrate the importance of the use of immunological markers for the accurate diagnosis of lymphoma.
- Published
- 1987
- Full Text
- View/download PDF
31. Factor VII and fibrinolytic response to deamino-8-D-argenine vasopressin in normal subjects and dissociate response in some patients with haemophilia and von Willebrand's disease.
- Author
-
Ludlam CA, Peake IR, Allen N, Davies BL, Furlong RA, and Bloom AL
- Subjects
- Adolescent, Adult, Aged, Antigens analysis, Factor VIII immunology, Female, Fibrinolysis drug effects, Humans, Male, Middle Aged, Time Factors, Arginine Vasopressin pharmacology, Deamino Arginine Vasopressin pharmacology, Factor VIII metabolism, Hemophilia A blood, Plasminogen Activators blood, von Willebrand Diseases blood
- Abstract
Deamino-8-D-argenine vasopressin (DDAVP) was given by intravenous infusion to normal subjects, haemophiliacs and patients with von Willebrand's disease (vWd) and the factor VIII and plasminogen activator response was studied. In normal subjects and most patients with mild haemophilia and mild (intermediate) von Willebrand's disease there was an increase in plasminogen activator and all factor VIII related activities. In patients with mild vWd the prolonged bleeding time was shortened by DDAVP despite only a modest rise in factor VIII related Ristocetin cofactor activity (VIIIR:RiCoF). Sub-groups of patients have been characterized in whom atypical responses was observed. In two brothers with clinically severe haemophilia, but with 5--6 u/dl procoagulant factor VIII (VIIIC), there was an increase in VIIIC but no rise of the corresponding antigen, suggesting increased release of an antigenically abnormal poorly functioning molecule. A patient with intermediate vWd was studied in whom neither DDAVP, adrenaline infusion, nor venous occlusion resulted in an increase in either plasminogen activator or factor VIII related antigen (VIIRAg), although there was a significant increase in VIIIC. In a further patient with severe vWd, DDAVP failed to elicit any plasminogen activator or VIII response. The results obtained from these two patients suggested that in some individuals the presumed endothelial cell abnormality in vWd may be more extensive than a defect in VIIIRAg synthesis. Sub-groups of patients have been identified for whom treatment with factor VIII concentrates would be more appropriate than DDAVP prior to minor surgery.
- Published
- 1980
- Full Text
- View/download PDF
32. Studies on liberation of beta-thromboglobulin from human platelets in vitro.
- Author
-
Ludlam CA and Cash JD
- Subjects
- Anticoagulants pharmacology, Blood Preservation, Centrifugation, Edetic Acid pharmacology, Humans, Prostaglandins E pharmacology, Temperature, Theophylline pharmacology, Beta-Globulins metabolism, Blood Platelets
- Abstract
A platelet specific protein, beta-thromboglobulin, is liberated during the preparation of platelet poor plasma. Using combinations of different anticoagulant and anti-platelet compounds, this release can be significantly reduced. The best results were obtained when native blood was collected as soon as possible into a mixture of EDTA, prostaglandin E1 and theophylline and maintained and processed at a temperature between 0 and 4 degrees C. These technical innovations have permitted the use of a radioimmunoassay for beta-thromboglobulin on plasma samples in clinical practice.
- Published
- 1976
- Full Text
- View/download PDF
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