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Biomedical subjects

Y Sultan

Publications and source records attributed to Y Sultan.

At least 91 records · Page 5Linked to original sources
PubMed1990

Treatment of factor VIII inhibitors.

Factor VIII inhibitors are antibodies of the IgG class that neutralize the procoagulant activity of FVIII. They arise as alloantibodies in multitransfused haemophilia A patients and spontaneously in some individuals. Therapeutic strategy must be separated into two concepts: treatment of bleeding episodes and treatment of the inhibitor itself. Treatment of an haemorrhagic complication is dependent on the inhibitor titre and the status of the patient as a 'high' or 'low' responder. The choice has to be made between massive amounts of human FVIII concentrate, porcine FVIII and plasma preparations with 'bypassing' activity. Adjuvant therapy such as plasma exchange or extracorporeal passage of plasma over a Protein A sepharose column might be helpful. More recent products are still under evaluation such as FVIIa or recombinant tissue factor. Intravenous immunoglobulins have proven to be helpful mainly in patients with spontaneous inhibitors. Treatment of the inhibitor itself must be started as soon as possible. Several approaches are being used, immunosuppressive therapy or induction of immune tolerance using high intermediate or low doses of FVIII concentrate.

Antibodies↗
PubMed1989

The concept of anti-idiotypic regulation of selected autoimmune diseases by intravenous immunoglobulin.

Evidence that physiological control of human humoral autoimmune reactions depends, at least in part, on the formation of anti-idiotypic antibodies is accumulating. Upon binding to the corresponding idiotypes, anti-idiotypes will prevent autoantibodies from reacting with the primary antigen and/or eventually expedite removal of autoantibodies from the circulation and down-regulate their formation. In patients with autoantibodies against clotting factor VIII:C or fibrinogen, clinical improvement was associated with formation of anti-idiotypes against the autoantibodies. In addition, iv immunoglobulin (IVIg) preparations derived from plasma pools of thousands of healthy donors expressed anti-idiotypes against such autoantibodies as anti-clotting factor VIII:C, antithyroglobulin, and anti-intrinsic factor, but the specificity of the anti-idiotypes appears to be restricted for particular idiotypes. This explains why not all patients are responders to therapeutic intervention with IVIg. On one hand, definite in vitro neutralization of autoantibody activity by IVIg added in multiple proportions is not followed infallibly by in vivo response, and on the other hand, a good therapeutic effect often lasts long beyond normal half-lives of infused IVIg. The present overview compares the authors' own work with that described in recently published literature on exploring anti-idiotypy in therapy.

Antibodies, Anti-Idiotypic↗
PubMed1989

Dexamethasone treatment for bacterial meningitis in children and adults.

Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content.

Adult↗
PubMed1989

Platelet aggregation induced by type IIb platelet von Willebrand factor.

Platelet lysates from five patients with a form of type IIb von Willebrand's disease (vWd), associated with spontaneous platelet aggregation and thrombocytopenia, induced platelet aggregation of normal and other vWd's platelet-rich plasma (PRP). Platelet lysate from normals, type I or type IIa vWd did not cause platelet aggregation of normal PRP. When polyclonal monospecific antibodies directed against plasma von Willebrand factor (vWf) were incubated with the type IIb platelet lysate, they inhibited the platelet aggregation. Monoclonal antibodies directed against the glycoprotein (GP) Ib binding domain of plasma vWf incubated with the type IIb platelet lysate did not inhibit the platelet aggregation. Normal platelets suspended in afibrinogenaemic plasma did not aggregate when type IIb vWd platelet lysate was added. Normal platelets incubated with monoclonal antibodies directed against the fibrinogen and vWf binding site(s) on the GPIIb/IIIa were not aggregated by the type IIb platelet lysate. Bernard-Soulier PRP aggregated when type IIb vWd platelet lysate was added, while Glanzmann's thrombasthenic platelets did not. Peptides containing the RGDS sequence or the sequence of the carboxy terminal 15 amino acids of the gamma chain of fibrinogen inhibited the type IIb vWd platelet lysate-induced platelet aggregation. These data suggest that type IIb platelet vWf can cause platelet aggregation of PRP without the addition of any agonist. This interaction is different from that observed with the plasma vWf from these patients.

Antibodies, Monoclonal↗
PubMed1988

Tissue plasminogen activator in human megakaryocytes and platelets: immunocytochemical localization, immunoblotting and zymographic analysis.

Two approaches were used to identify and characterize the presence of tissue plasminogen activator (t-PA) in megakaryocytes and platelets. We investigated the fibrinolytic activity of human megakaryocytes (MK) and platelets. The presence of t-PA antigen in megakaryocytes and platelets was demonstrated using immunocytochemical techniques and polyclonal or monoclonal antibodies specific for t-PA. When cells were applied to fibrin plates, lysis zones developed around isolated human megakaryocytes, whereas no fibrinolytic activity appeared when either intact washed platelets or platelet lysate were deposited. After SDS-PAGE of platelet and MK extracts (Triton X-100) immunoblotting and peroxidase staining identified t-PA antigen in several bands. Zymographic analysis of SDS-PAGE carried out on fibrin film overlays identified one or two zones corresponding to free or complexed t-PA. These results indicate that t-PA is present in platelets as well as in the precursor cells, however, in platelets, t-PA may not be immediately available for plasminogen activation and fibrin degradation. From our findings and from previous work of others, it appears that platelets may either activate or inhibit the fibrinolytic system. Therefore the conditions of plasminogen activation by platelet t-PA and plasmin inhibition by platelet alpha 2-antiplasmin or other inhibitors have to be precised before the role of platelets in clot dissolution is understood. The physiological role of platelets in fibrinolysis and clot dissolution remains unclear. In 1953, the antifibrinolytic activity of blood platelets was demonstrated and in the early 1960's a fibrinolytic activity, increasing with platelet concentration in the experimental system, was shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1988

Fibrinolysis abnormalities in systemic lupus erythematosus and their relation to vasculitis.

Fibrinolysis was evaluated in 16 women with SLE, who were divided into three groups of increasing disease severity according to their past history, and in 10 normal subjects. Fibrinolysis parameters assessed were tissue-type plasminogen activator (t-PA) activity in plasma and in euglobulin fractions and rapid plasminogen activator inhibitor activity. All parameters were evaluated before and after venous occlusion to assess endothelial cell t-PA release in response to localized anoxia. Markers of deficient fibrinolysis were persistently undetectable t-PA activity and increased rapid plasminogen activator inhibitor activity after venous occlusion. Defective fibrinolysis was correlated with disease severity; it was noted only in patients with severe or moderate disease and in no patients with mild disease or in controls. Fibrinolysis abnormalities were independent of disease activity, suggesting that vascular endothelium injuries occurring during flare-ups persist during inactive phases of the disease. No correlation was found between fibrinolysis abnormalities and disease duration, corticosteroid administration, or the presence of lupus anticoagulant or anticardiolipin antibodies. These data support the hypothesis of parallelism between the severity of vascular injuries, suggested by deficient fibrinolysis, and the severity of clinical manifestations in SLE.

Adult↗
PubMed1988

A dynamic test to investigate potential tissue plasminogen activator activity. Comparison of deamino-8-D-argininevasopressin with venous occlusion in normal subjects and patients.

Fibrinolysis dependent on the release of tissue plasminogen activator (t-PA) can only be explored after stimulation eliciting the release of t-PA from endothelial cells. The choice of the stimulus and test assay is of utmost importance in discriminating patients at risk for persistent thrombosis and in identifying acquired or genetic abnormalities of t-PA synthesis or release from endothelial cells in pathologic conditions. The present study was designed to compare the efficacy and reproducibility of the fibrinolytic response to desmopressin acetate (deamino-8-D-argininevasopressin) (DDAVP) by use of various routes of administration with the response to the venous occlusion test. Nine healthy male volunteers were randomly administered intravenous desmopressin acetate, intranasal drops and intranasal spray. The results from tests of euglobulin lysis time, t-PA activity, t-PA antigen levels, and t-PA fast-acting inhibitor (plasminogen activator inhibitor [PAI]) level were compared with those obtained after venous occlusion. The only test that elicited the release of free t-PA activity in the circulation in all volunteers was the intravenous administration of 0.4 microgram/kg desmopressin acetate, and the most reliable test assay was t-PA activity measured in the euglobulin fraction of plasma. Intravenous desmopressin acetate induced the release of large amounts of t-PA in most cases and caused a significant fall in PAI. Other routes of administration of desmopressin acetate, along with venous occlusion, identified many nonresponders who proved to be false negative. The relevance of these data was demonstrated in a study in nine patients with thromboembolic phenomenon or related disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1988

Clinical and biological survey of haemophilia A and B patients infused with French heat-treated concentrates.

The efficiency of heat treatment procedures of factor VIII and factor IX concentrates, prepared from voluntary, non-paid donors by three French Blood Transfusion Centres, on the inactivation of HIV and non-A, non-B hepatitis (NANB) viruses was assessed. Some 43 patients (26 haemophilia A, 17 haemophilia B) were followed for at least 1 year by testing for HIV antibodies and alanine aminotransferase (ALT). No HIV seroconversion was observed indicating that heat treatment was completely efficient. Among 26 haemophiliacs, 6 (4 haemophilia A, 2 haemophilia B) presented an elevation in ALT, indicating only a 75% reduction of NANB viral contamination.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Anti-idiotypes against autoantibodies and alloantibodies to VIII:C (anti-haemophilic factor) are present in therapeutic polyspecific normal immunoglobulins.

Therapeutic, polyspecific, normal immunoglobulins (IVIg) suppress anti-factor VIII (VIII:C) activity of anti-VIII:c autoantibodies in vivo and in vitro. In the present study anti-VIII:C activity was found to be inhibited by two different preparations of IVIg in the plasma of three of four patients with autoantibodies and two of three patients with alloantibodies. F(ab')2 fragments from IVIg inhibited anti-VIII:C activity in F(ab')2 fragments from the plasma of the patients. In patients in whom anti-VIII:C activity was inhibited by IVIg, anti-VIII:C F(ab')2 antibodies were specifically retained on an affinity column of Sepharose-bound F(ab')2 from IVIg. In patients in whom anti-VIII:C activity was not suppressed by IVIg in vitro, no binding of anti-VIII:C antibodies to Sepharose-bound IVIg was observed. In a patient in whom anti-VIII:C activity was only suppressed by one preparation of IVIg, specific binding of anti-VIII:C antibodies was only observed with that preparation but not with another. These results indicate that IVIg contain anti-idiotypes against autoantibodies and alloantibodies to VIII:C. The capacity of IVIg to inhibit anti-VIII:C activity in vitro is directly related to the presence of demonstrable anti-idiotypes against anti-VIII:C antibodies. The finding of anti-idiotypes against anti-VIII:C alloantibodies in IVIg suggests that, in addition to autoantibodies, some alloantibodies may be suppressed in vivo by IVIg.

Adult↗
PubMed1987

A variant of type II von Willebrand disease with an abnormal triplet structure and discordant effects of protease inhibitors on plasma and platelet von Willebrand factor structure.

We have characterized the plasma and platelet von Willebrand factor (vWf) multimeric structure of a patient with von Willebrand disease (vWd) as having a long bleeding time, no aggregation of her platelet-rich plasma (PRP) to ristocetin, and very low plasma and platelet von Willebrand antigen (vWf Ag) and vWf activity. The abnormalities of the plasma and platelet vWf have not been previously described. In particular, the patient's plasma and platelet vWf lacked the intermediate and largest vWf multimers and the slowest migrating minor band (band 1) of the triplet was markedly diminished compared to the major band (band 2) and the fastest migrating band of the triplet (band 3). A similar multimeric structure was seen in the platelet vWf. Collection of the patient's blood in protease inhibitors prior to the analysis of the platelet and plasma vWf structure revealed that the plasma vWf multimeric structure did not change, while the patient's platelet vWf showed a marked change with the appearance of the intermediate and large multimers and almost total disappearance of the abnormal multimeric structure. Direct comparison of this patient's plasma with previously reported cases of type IIA, IIC, and IID revealed marked differences in their multimeric organization compared to our patient. Employing the presently accepted convention, we have designated this variant type of vWd type IIG.

Blood Platelets↗
PubMed1987

Recovery from anti-VIII:C (antihemophilic factor) autoimmune disease is dependent on generation of antiidiotypes against anti-VIII:C autoantibodies.

Plasma samples obtained from a patient 6 wk, 6 months, and 4 yr after recovery from anti-VIII:C (anti-hemophilic factor, where VIII:C = factor VIII procoagulant activity) autoimmune disease were found to contain antibodies that inhibited anti-VIII:C activity in the patient's prerecovery plasma and in the plasma of two other patients with anti-VIII:C autoantibodies. F(ab')2 fragments from postrecovery IgG suppressed anti-VIII:C activity in F(ab')2 fragments from prerecovery IgG within a narrow range of molar ratios. Anti-VIII:C activity in F(ab')2 autoantibodies was also inhibited by F(ab')2 fragments from polyspecific therapeutic immunoglobulins prepared from a large pool of normal donors (IVIg). IgG from prerecovery plasma bound to F(ab')2 from postrecovery IgG and to F(ab')2 from IVIg, as assessed by ELISA. Affinity chromatography experiments demonstrated that F(ab')2 from postrecovery IgG preferentially bound anti-VIII:C antibodies among F(ab')2 fragments from prerecovery plasma containing anti-VIII:C autoantibodies. F(ab')2 from prerecovery plasma bound in higher amounts to postrecovery F(ab')2 than to IVIg. Insolubilized F(ab')2 fragments from postrecovery plasma also bound F(ab')2 fragments prepared from the plasma of another patient with anti-VIII:C autoimmune disease, although in lesser amounts than the patient's own prerecovery anti-VIII:C F(ab')2 antibodies. These observations suggest that human anti-VIII:C autoantibodies share idiotypic determinants and that spontaneous recovery from anti-VIII:C autoimmune disease occurs through idiotypic suppression of autoantibodies. In patients who recover from autoimmune disease and in patients in whom autoantibodies have been suppressed by infusions of IVIg, antiidiotypic antibodies, possibly by providing internal images of the antigen, may have shifted the immune system toward the steady-state equilibrium that prevents autoimmunity in normal individuals.

Adult↗
PubMed1987

Absence of functional activity of tissue plasminogen activator in patients with severe forms of von Willebrand's disease.

Some patients with von Willebrand's disease do not respond to stimuli such as venous occlusion and infusion of a vasopressin analogue DDAVP. In these patients, fibrinolytic activity is not enhanced and von Willebrand's factor is not released into the blood. Skin biopsies and cryostat sections were used to study the fibrinolytic activity of skin vessels and localization of tissue plasminogen activator (t-PA) in three patients with severe form of von Willebrand's disease. On fibrin films, no fibrinolysis developed around the skin vessels of the patients; however, using specific polyclonal and monoclonal antibodies to t-PA, and peroxidase coupled specific IgG, presence of t-PA antigen was demonstrated in endothelial cells (EC) of all of them. In plasma no t-PA activity was detected either before or after venous occlusion although t-PA inhibitor activity was in a normal range. Small amounts of t-PA antigen was measured in blood by ELISA. From these results, it is concluded that in patients with severe forms of von Willebrand's disease, t-PA present in EC is not functional and can not transform plasminogen into plasmin.

Adolescent↗
PubMed1987

HLA typing in heavily transfused haemophiliacs with or without antibodies against human immunodeficiency virus (HIV).

HLA-A, B, DR antigens were determined in 46 patients, heavily transfused with blood products. Patients were 44 haemophiliacs, one case of afibrinogenemia and one case of von Willebrand's disease. Thirty-three patients had HIV antibodies. No significant difference for HLA antigen frequencies was observed in haemophiliacs with or without HIV antibodies, nor between haemophiliacs and a control population.

Adolescent↗
PubMed1987

The role of HIV infectivity and composition of factor VIII concentrates on the immunity of haemophiliacs positive for HIV antibodies.

Forty-six subjects (44 HIV antibody-positive) with some degree of immune deficiency (at least TH/TS ratio below 1) were randomly distributed into 4 treatment groups. Each group was assigned to 1 of 4 products to be used exclusively for a 1-year period: 1 concentrate was of intermediate purity and not heat-treated, and 3 were heat-treated in order to inactivate HIV, 2 of them being of higher purity. At 4-6-month intervals, check-ups, including as markers clinical examination, platelet, lymphocyte and T cell subset counts, IgG levels and delayed hypersensitivity test, were carried out. At entry as well as at the end of the study, groups were not statistically distinguishable. No intra- nor inter-group differences were demonstrable for any of the markers. In contrast, using a scoring system for each marker and the results of check-up at entry as reference, significant differences between groups appeared on subsequent check-ups. Patients receiving intermediate-purity factor VIII, whether heat-treated or not, were mostly steady, while groups receiving heat-treated concentrates of a higher purity significantly worsened. This surprising outcome was no related to differences in anti-HIV titers or specificities. From this study, the potential long-term predictive value of this scoring system could not be established.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Epidemiology of HIV infection in multitransfused hemophilic patients in France. French Study Group in Hemophilia.

A total of 27 hemophilia centers treating patients all over France responded to a questionnaire about the progression of HIV infection in multitransfused patients. Information from 2,049 hemophilic patients was collected. The prevalence of HIV infection in French hemophiliacs was 48%, the same as the percentage in 1985, demonstrating that the methods of viral inactivation of concentrates and screening of blood donors are efficient. However, the number of patients with AIDS increased from 14 to 26 and patients dead from opportunistic infection from 47 to 14 in 1 year. There is also evidence of clinical symptoms of AIDS-related complex and biological symptoms of immunodeficiency in this population of seropositive French hemophiliacs.

Acquired Immunodeficiency Syndrome↗