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Biomedical subjects

Y Sultan

Publications and source records attributed to Y Sultan.

At least 73 records · Page 4Linked to original sources

Aztreonam compared to chloramphenicol in the treatment of enteric fevers.

Fifty-seven patients, twenty-six males and thirty-one females, aged 6 to 50 years (mean 12.6 years) with proven Salmonella typhi or S. paratyphi A septicaemia, were treated in an open randomized parallel study with either aztreonam or chloramphenicol. Aztreonam was given intramuscularly at a level of 50 to 80 mg/kg body weight per dose every 8 h for 7 days to thirty patients. Chloramphenicol was given orally in a dose of 50 to 70 mg/kg body weight every 6 h for 12 days to twenty-seven patients. All patients responded rapidly to treatment, becoming afebrile and asymptomatic within 5.5 to 6.4 days. Only one patient on aztreonam relapsed following treatment, whereas three patients relapsed after chloramphenicol treatment. There were no serious side effects with either drug.

Administration, Oral↗

Impaired fibrinolytic response to DDAVP in patients with von Willebrand's disease.

The fibrinolytic response after infusion of 1-deamino-8-d-arginine vasopressin (DDAVP) was examined in 4 patients with the severe form and 17 patients with the moderate form of Von Willebrand's disease (VWd) and compared to that of 9 normal subjects. Tissue plasminogen activator (t-PA) antigen (Ag) and activity and tissue plasminogen activator inhibitor (PAI) were measured before and after DDAVP. t-PA Ag was found to be significantly higher before DDAVP in patients than in controls. No release of t-PA Ag was observed in the 4 patients with the severe form of VWd but increased release was observed in patients with moderate forms. However, t-PA released into the circulation in these 17 patients had a lower functional activity as compared to that of normal subjects. PAI was significantly lower in patients before DDAVP than in normal subjects and the decrease in PAI after DDAVP was significantly less in patients than in controls. It is concluded from this study that patients with VWd have an abnormal fibrinolytic response after stimulation regardless of the severity of the disease. Furthermore, the results suggest either that patients with VWd have a double defect in VWF and tissue plasminogen activator or that the primary deficiency of VWF influences the synthesis and/or release of t-PA by endothelial cells.

Adolescent↗

Intravenous immunoglobulin in the treatment of spontaneously acquired factor VIII:C inhibitors.

Intravenous immunoglobulin (IV Ig) is useful in most patients with spontaneous factor VIII:C (FVIII:C) inhibitors, but some complete failures also are observed. Among patients responding to this therapy, decreases in FVIII:C autoantibody titer occurs within 24-48 hours and may lead to suppression of inhibitor activity. The prolonged response observed in some cases suggest an effect on autoantibody synthesis. The immediate decrease in FVIII:C inhibitory activity after IV Ig infusion indicates a direct interaction between IV Ig and the autoantibody. This effect is reproducible in vitro by mixing the patient's plasma and Ig at an appropriate molar ratio, which differs in each patient. Similarly, incubation of Ig with F(ab)'2 fragments of a patient's IgG and Ig reproduces inhibition, and this result indicates that the interaction is mediated by antigen binding sites (epitopes) on the immunoglobulins. The suggestion is that an idiotype- anti-idiotype mechanism must be at work. The origin of such anti-idiotypes in Ig prepared from pooled plasma of several thousand blood donors is unclear. The F(ab)'2 fragments were prepared from individual blood donors and tested in similar experiments with F(ab)'2 fragments of three distinct spontaneous FVIII:C inhibitors. The plasma level of anti-idiotypic antibodies reacting with FVIII:C inhibitors varied according to age and gender.

Antibodies, Anti-Idiotypic↗

Dexamethasone adjunctive treatment for tuberculous meningitis.

During a 5-year period, 280 of 2010 patients admitted to the meningitis ward of a referral hospital in Cairo, Egypt, were clinically diagnosed as having tuberculous meningitis and were treated with either antituberculous chemotherapy and dexamethasone or antituberculous chemotherapy alone. Fatality rates and neurologic sequelae were compared for the 2 treatment groups in the 160 patients who had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. The overall mortality rate of 51% reflects the delay in receiving appropriate therapy (79% with symptoms for more than 2 weeks) and the severity of illness on admission (56% in coma, 39% drowsy). The fatality rate was significantly lower in the group receiving dexamethasone (43% vs. 59%, P less than 0.05), particularly in the drowsy patients (15% vs. 40% P less than 0.04), and in patients surviving long enough to receive at least 10 days of treatment (14% vs. 33%, P less than 0.02). Development of neurologic complications after initiation of therapy (4 vs. 10) and permanent sequelae (6 vs. 13) were significantly lower in the dexamethasone-treated group (P less than 0.02).

Adolescent↗

Involvement of heparin cofactor II in chymotrypsin neutralization and in the pancreatic proteinase-antiproteinase interaction during acute pancreatitis in man.

Heparin cofactor II is a proteinase inhibitor which inhibits both chymotrypsin and thrombin, and displays great similarities with antithrombin III, the main inhibitor of thrombin in human plasma. Since acute pancreatitis is known to be associated with modification of the proteinase-antiproteinase equilibrium, we studied heparin cofactor II and antithrombin III as well as other biochemical and haematological parameters in 10 patients experiencing attacks of acute pancreatitis. Heparin cofactor II activity decreased during the first week of illness, while its antigen concentration remained subnormal. This discrepancy between antigen concentration and activity which persisted during the first week of illness was due both to complex formation of heparin cofactor II with its target proteinases and to partial proteolysis of the inhibitor. Heparin cofactor II was shown to form a complex with chymotrypsin in the plasma of such patients. Antithrombin III levels remained unchanged throughout the study, with no discrepancy between its activity and antigen concentration. No modification of haemostasis was shown either, except for a rise in the fibrinogen level during the first days of illness. It is concluded that, unlike antithrombin III, heparin cofactor II is involved in the proteinase-inhibitor equilibrium in patients with acute pancreatitis, and that heparin cofactor II might react as an inhibitor of pancreatic proteinases rather than an inhibitor of thrombin.

Acute Disease↗

Autoantibodies against all the phospholipids: a comparative systematic study with systemic lupus erythematosus and healthy sera.

The sera of systemic lupus erythematosus patients were tested by ELISA for the presence of autoantibodies against all the phospholipids: cardiolipin, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylserine. The quantity of phospholipid coated (in comparison with that initially deposited) on the microtitration plates was precisely evaluated in order to determine if the results (absorbance values) obtained for each phospholipid could be compared directly. The systemic lupus erythematosus sera tested gave positive results for all the phospholipids. The highest level of autoantibodies was observed with phosphatidic acid followed by phosphatidylserine, phosphatidylinositol, cardiolipin, phosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. The sera seemed to contain antibodies directed either against all the 8 phospholipids tested or more specifically against one or two phospholipids. The results were compared with those obtained with 17 healthy sera. Much lower values were obtained for the sera of healthy subjects, the majority of which showed a weak binding, similar for all the phospholipids. These results suggest that the anti-phospholipid autoantibodies present in systemic lupus erythematosus sera are significantly higher than those of healthy subjects. It is concluded that in the investigation of anti-phospholipid antibodies, tests should be carried out for all the phospholipids.

Antibody Specificity↗

Hemophilia in 1991.

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Blood Coagulation Factors↗

Investigation of factor VIII:C gene restriction fragment length polymorphisms and search for deletions in hemophiliac subjects in Algeria.

The frequency of alleles for intragenic (intron 17 and intron 25) and extragenic (DXS15 and DXS52) F8C RFLPs was investigated in the Algerian population. Altogether 287 X chromosomes (97 males and 95 females) were studied. The allele frequencies found with the two intragenic F8C RFLPs were not substantially different from those reported in a Mediterranean population. At the highly polymorphic extragenic DXS52 locus the distribution in Algeria differed from that found in France. A new allele (14 kb), called 1 DZ, was found in 3.1% of the chromosomes. Fifty-one families with hemophilia A were studied with the same probes (374 subjects). Of the females, 94% were informative for at least one intra- or extragenic RFLP. Two recombinations were found between DXS52 and F8C, of which one occurred between the DXS15, DXS52 block and F8C, indicating that the two anonymous loci are on the same side of the F8C gene. Only two obvious gene deletions were observed in 73 unrelated hemophiliacs: one encompassed exons 14-22 (about 4.3 kb of cDNA and 36 kb of genomic DNA); the other removed the last exon (exon 26, representing 2 kb of cDNA).

Algeria↗

Tissue-plasminogen activator RNA detected in megakaryocytes by in situ hybridization and biotinylated probe.

Tissue-plasminogen activator (t-PA) has been identified in human megakaryocytes isolated from human rib fragments or from culture cells. The presence of t-PA antigen in the endoplasmic reticulum of mature cells was demonstrated by ultrastructural immunochemistry. These results suggest that t-PA can be synthesized by megakaryocytes as well as by vascular endothelial cells. In order to confirm this possibility, in situ hybridization using antisense RNA biotinylated probe was used in megakaryocyte culture at different steps of maturation. The presence of t-PA-RNA was clearly demonstrated at an early step of differentiation. Biotin staining was enhanced in mature cells and this was correlated with the detection of t-PA antigen by immunocytochemistry.

Cells, Cultured↗

A monoclonal anti-idiotypic antibody against the antigen-combining site of anti-factor VIII autoantibodies defines and idiotope that is recognized by normal human polyspecific immunoglobulins for therapeutic use (IVIg).

The present study demonstrates that normal human immunoglobulins for therapeutic use (IVIg) contain anti-idiotypes that recognize an antigen-binding site-related idiotope of anti-Factor VIII autoantibodies defined by a mouse monoclonal antibody (MoAb). MoAb 20F2 was obtained by immunizing a mouse with affinity-purified anti-Factor VIII F(ab')2 fragments prepared from the IgG fraction of a patient with anti-Factor VIII autoantibodies. The monoclonal antibody was directed against an overlapping epitope on the antigen-binding site of the patient's anti-Factor VIII autoantibodies and the CH1 domain of human IgG1. The anti-Factor VIII activity of the patients's autoantibodies was neutralized by MoAb 20F2 in a dose-dependent manner. A fraction of the patient's anti-Factor VIII auto-antibodies was specifically retained on affinity columns of Sepharose-bound MoAb 20F2; anti-Factor VIII activity of antibodies in this fraction was totally inhibited by MoAb 20F2, indicating an idiotopic homogeneity of retained anti-Factor VIII autoantibodies. IVIg inhibited the anti-Factor VIII activity of 20F2 idiotope-positive F(ab')2 antibodies, thus indicating that the IVIg recognize the 20F2 idiotope on patient's autoantibodies. These observations further support the concept of the presence in IVIg of anti-idiotypes against autoantibodies associated with human autoimmune diseases.

Animals↗

Factor IX concentrate versus prothrombin complex concentrate for the treatment of hemophilia B during surgery.

Hemophilia B patients are usually treated for the prevention and control of bleeding episodes with a plasma derivative containing the four vitamin K-dependent clotting factors (PPSB). Prothrombin complex concentrate and the French PPSB concentrate are known to be thrombogenic when used in long-term treatment of surgical patients. The present study reports two cases of thrombotic episodes following surgery in PPSB-treated hemophilia B patients. Since 1986, there has been available a factor IX (FIX) concentrate depleted of the other vitamin K-dependent clotting factors and virally inactivated by the solvent-detergent method. This preparation has been used as replacement therapy in six patients with severe hemophilia B who were to undergo orthopedic surgery. The management of the patients before and after operation was without any thrombotic complication or undesirable side effects. The present study suggests that there is a need for an FIX preparation devoid of the other vitamin K-dependent clotting factors for long-term therapy of hemophilia B patients.

Adult↗

Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations in the patient.

Mononuclear cells were obtained from 71 human immunodeficiency virus type 1 (HIV-1) seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with CD4 lymphocytes greater than 550 per mm3 (group A, 35 patients) or as patients with AIDS, AIDS-related illnesses, or CD4 lymphocytes less than 400 per mm3 (group B, 36 patients). After 1-5 years of follow-up, 13 patients of group A had essentially retained their initial status (asymptomatics); the 22 others had suffered clinical or immunological deterioration (progressors). Frozen cells were thawed and submitted to lethal gamma-irradiation in vitro (4500 rads; 1 rad = 0.01 Gy) before they were cultured with normal phytohemagglutinin-stimulated lymphocytes to determine radiation-resistant HIV expression ex vivo (R-HEV). HIV antigenemia correlated with R-HEV values in 142 samples (r = 0.92, P less than 0.001) but was a less sensitive predictor of disease than R-HEV. R-HEV was detected in all specimens from patients with major AIDS-related illnesses or HIV-associated CD4 lymphopenia. In 77% of the progressors from group A, R-HEV detection preceded the onset of AIDS-associated disease or CD4 lymphopenia by 1 year (average). Conversely, R-HEV was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2-5 years. Thus, persistently low HIV expression in vivo predicted a nondiseased state, whereas higher HIV expression levels seemed necessary for disease to occur. These data indicate that R-HEV is related to productive HIV infection in vivo, the latter acting as a determinant of AIDS-related illnesses. In view of this, measurement of HIV expression levels in the patient should be useful in antiviral efficacy trials.

Acquired Immunodeficiency Syndrome↗

Activation of platelets, coagulation and fibrinolysis in patients on long-term haemodialysis: influence of cuprophan and polyacrylonitrile membranes.

This study was designed to evaluate platelet activation, enhancement of coagulation and fibrinolysis in patients with chronic renal failure on long-term haemodialysis. Beta thromboglobulin (BTG), platelet factor 4 (PF4), fibrinopeptide A, tissue plasminogen activator (t-PA) activity and antigen, tissue plasminogen activator inhibitor (PAI), fibrin, and fibrinogen degradation products were studied during dialysis. The influence of two types of membrane on these parameters was also evaluated. The patients comprised 24 individuals on long-term haemodialysis on either cuprophan membrane (CUP) (12 patients) or polyacrylonitrile membrane (AN 69) (12 patients). Blood samples were collected before, at 15 min, and at the end of dialysis. The results demonstrated that platelet activation was permanent and increased during haemodialysis. However, no difference could be demonstrated between patients treated on CUP and patients treated on AN 69. Coagulation was also enhanced permanently but did not show modification during haemodialysis. Fibrinolysis was activated at the end of haemodialysis in half the patients, but again no difference could be demonstrated between patients treated on AN 69 and CUP membranes. It was concluded that the process of haemodialysis itself enhanced platelet activation, coagulation, and fibrinolysis but that both membranes were of equal effect.

Acrylic Resins↗

Anti idiotypic recognition of auto and allo antibodies to factor VIII by immunoglobulin preparations from single blood donors and large plasma pool.

Therapeutic immunoglobulins from commercial origin were administered to patients with allo and auto antibodies to factor VIII. The protocol used was similar to the prescription suggested for ITP, 0.4 g/kg body weight for five consecutive days. In patients with auto antibodies two kinds of effects were observed: A direct interaction between IVIg and the factor VIII inhibitor and long term interaction on antibody synthesis. The direct interaction observed in vivo was demonstrated to be mediated through Fab'2 fragments of both idiotypic interaction. This was also demonstrated using binding experiments and affinity chromatography experiments: Fab'2 fragments of IVIg were coupled to sepharose and Fab'2 fragments of patients IgG with allo and auto antibodies to Factor VIII were circulated through the column. The recovery of anti Factor VIII antibodies after elution was possible in 2 cases of allo antibodies out of 3 tested and 3 cases of auto antibodies out of 4. The question of anti idiotypes against factor VIII inhibitors in single individuals was investigated. IgG and Fab'2 fragments from single blood donors were isolated and tested for their inhibitory capacity against Fab'2 fragments of three different auto antibodies. The results did not show statistical differences between males and females however in the group of male blood donors, aging was a positive parameter for the presence of anti idiotypic antibodies against factor VIII inhibitors. Anti idiotypic antibodies against factor VIII inhibitors were present in 17.2% of the blood donor tested.

Antibodies, Anti-Idiotypic↗