Early paternity and relapse after bone marrow transplantation.
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Adult↗
Biomedical subjects
J J Huart
Publications and source records attributed to J J Huart.
[Industrial pasteurization of plasma and criteria of quality].
The approach followed in the design of a large-scale pasteurization treatment (60 degrees C for 10 hours in the liquid state) of fresh frozen plasma is presented. Various aspects thought to influence the viral safety of such a product are discussed. They are based largely upon the fact that, although it is subjected to a specific viral inactivation treatment, this plasma does not benefit from any fractionation steps known to participate in the potential elimination of infectious agents during the manufacture of plasma derivatives. Consequently, the plasma is obtained from regular plasmapheresis donors, and the plasma donations used to make the pool must be negative for anti-HIV-1 and -2, anti-HCV, anti-HBc, anti-HTLV-1 and -2, HBs antigen and parvovirus B19 antigen, and have a normal level of ALT. The batch size is limited to 100 plasma units to limit the potential infectious risk associated with very large batches, especially if an infectious agent, resistant to pasteurization, is present. Pasteurization has been chosen for this procedure, as applied to plasma derivatives, has been shown to inactivate a broad spectrum of viruses, both enveloped and non-enveloped. The process is relatively simple. The frozen plasma units are opened, and the plasmas are mixed and thawed at 30 degrees C to avoid the formation of cryoprecipitate. The liquid plasma is transferred to a sterilized container and stabilizers are added. The mixture is then transferred to the pasteurization unit to be heat-treated at 60 degrees C for at least 10 hours under gentle mixing. Following cooling, the mixture is ultrafiltered to eliminate the stabilizers and to concentrate the plasma pool to its initial volume. The plasma is sterile-filtered, then dispensed into bottles and frozen. Virus validation of this pasteurization process, carried out by independent virology laboratories, have confirmed the ability of the process to inactivate more than 4 to 6 logs of non-enveloped or enveloped, DNA or RNA, viruses, including HIV-1 and Sindbis virus, in less than 5 hours of heat-treatment. The biological characteristics of the pasteurized plasma include a good preservation (75 to 95%) of the activity of clotting factors, including FI, FV, FVIII, FXI, and FXIII, and protease inhibitors. The overall clottability of the plasma, as expressed by the APTT, is almost unchanged.(ABSTRACT TRUNCATED AT 400 WORDS)
Blood Donors↗
Human monoclonal anti-D-induced clearance of human D-positive red cells in a chimpanzee model.
Two human monoclonal anti-Rh0(D) antibodies, one IgG1, and one IgG3, were tested for their ability to clear human D-positive red blood cells (RBCs) from chimpanzee circulation. Human RBCs (phenotype A1, R1r) from 1 donor were radiolabelled with chromium 51 and injected into 4 chimpanzees. One day later the control animal received isotonic saline whereas 2 animals received 400 micrograms of purified human monoclonal anti-D, either IgG1 or IgG3. The remaining animal received both antibodies together (200 micrograms of IgG1 and 200 micrograms of IgG3). Both individual antibody-mediated clearance of human D-positive cells and synergy was not observed when both antibodies were used in combination. IgG1 was slightly more effective than IgG3. This animal model is a suitable alternative for conducting in vivo experiments in human beings, especially at the preclinical study phase of monoclonal anti-D antibodies.
Animals↗
Double-blind, placebo-controlled trial of antithrombin III concentrates in septic shock with disseminated intravascular coagulation.
BACKGROUND: Septic shock is frequently complicated by a syndrome of disseminated intravascular coagulation (DIC). Numerous uncontrolled clinical studies have reported that antithrombin III (ATIII) substitution might prevent DIC and death in septic shock. METHODS: We conducted a randomized double-blind placebo-controlled trial in patients with a documented septic shock and DIC. The patients received either a placebo or ATIII (90 to 120 IU/kg in loading dose, then 90 to 120 IU/kg/d during 4 days). Administration of fresh frozen plasma, platelets, and fibrinogen concentrates was restricted to patients with hemorrhages and severe decreases in prothrombin time, platelet count, and fibrinogen levels. RESULTS: Thirty-five patients entered the study (18 placebo, 17 ATIII). Both groups were well balanced for all demographic, hemodynamic, and biologic data. Three patients were excluded before the treatment allocation code was broken. In the ATIII group, ATIII levels were rapidly corrected and remained over normal levels until day 10; sequential protein C and protein S levels were not modified. The duration of DIC was significantly reduced: in the ATIII group, 64 percent of patients were cured of DIC at day 2, and 71 percent were cured at the end of treatment vs in the placebo group, 11 percent (p < 0.01) and 33 percent (p < 0.05), respectively. In the 32 included patients, the mortality in ICU was reduced by 44 percent in the ATIII group (p = 0.22, NS). Care loads and transfusion requirements were not different. No side effect was observed. CONCLUSIONS: Mortality was reduced by 44 percent in this trial, but the difference did not reach the statistical significance. Circulating protein C and protein S levels were not modified by ATIII supplementation. High doses of ATIII concentrates significantly improved sepsis-induced DIC during septic shock. The trend toward improved survival suggests further randomized studies.
Antithrombin III↗
Improvement in HLA-DQB typing by PCR-RFLP: introduction of a constant restriction site in one of the primers for digestion control.
The PCR-RFLP method previously reported by Inoko is a powerful technique for HLA class II typing. The reliability of RFLP interpretation depends on complete digestion by restriction endonucleases using a modified primer with restriction sites as an internal digestion control. The use of restriction enzymes which recognize specific HLA DQB allelic variations makes HLA DQB genotyping possible.
Alleles↗
A pasteurized therapeutic plasma.
A process to subject pooled human plasma to a viral inactivation treatment by heating in the liquid state for 10 hrs at 60 degrees C (pasteurization) has been designed and evaluated. Activity recovered from clotting factors and protease inhibitors exceeded 80%. Overall clotting activity remained good. No activation of coagulation factors was detected. The process did not generate aggregates. No side effects (toxicity, hypotension, variation in heart rate, thrombogenicity) could be detected in animal models. Virus kill studies, using 7 lipid-enveloped and non-enveloped viruses including HIV-1 and Sindbis virus, revealed inactivation levels similar to those obtained for plasma derivatives. Thus, pasteurisation of human plasma can be achieved in conditions that allow good recovery of biological properties while ensuring a high degree of inactivation of lipid-enveloped and non-enveloped viruses.
Blood Banks↗
Use of human keratinocytes cultured on fibrin glue in the treatment of burn wounds.
Keratinocytes isolated from a small skin biopsy and cultured according to the method of Rheinwald and Green (Cell 1975, 6: 331) are able to undergo rapid expansion in vitro and have been used successfully in the treatment of burn wounds. One of the inconveniences of this method involves the transfer of the epidermal sheet from the culture flask onto the wound bed. One way to facilitate this process is to use fibrin glue (Biocol) as a culture bed for the keratinocytes. Burns are then grafted by simply placing the sheet of fibrin glue and keratinocytes onto the wound bed. This process has been successful in two patients, permanently covering areas of 720 cm2 and 5342 cm2. The newly formed epidermis was fully differentiated and histologically normal after 1 year. The efficiency of this improved, faster procedure could lead to a new approach in the treatment of extensive burn wounds.
Adult↗
[Post-transfusional cytomegalovirus infections: incidence and methods of prevention. CMV group of SNTS].
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Cell Separation↗
A highly purified factor VIII:c concentrate prepared from cryoprecipitate by ion-exchange chromatography.
A new ion-exchange chromatographic procedure has been developed to produce a highly purified factor VIII (FVIII) concentrate from plasma cryoprecipitate. Solubilized cryoprecipitate, after adsorption on aluminium hydroxide and cold precipitation, was treated with 0.3% tri(n-butyl)phosphate and 1% Tween 80 at 25 degrees C for at least 8 h to inactivate lipid-enveloped viruses. The fraction was then loaded onto a column packed with DEAE-Fractogel TSK 650 M and chromatographed. Most proteins and TnBP-Tween 80 flowed through the gel unretarded. FVIII:c, which bound to the gel, was eluted by increasing the ionic strength, then was directly filter-sterilized without ultrafiltration or addition of a protein stabilizer. Chromatographic recovery of FVIII:c was 80-90%. After freeze-drying, FVIII:c was at a concentration of 42.5 +/- 9.5 IU/ml and had a specific activity of 175.4 +/- 37.8 IU/mg (n = 40), corresponding to a purification factor of over 12,000 from plasma. The typical yield of the freeze-dried FVIII:c from cryoprecipitate was 55-65%. FVIII:c was stable for over 24 h at room temperature in the liquid state. The mean content of fibrinogen and immunoglobulin G was only 65 and 100 mg/l, respectively, corresponding to 1.4 and 2.3 mg/1,000 IU FVIII:c. This concentrate, which is much purer than traditional FVIII concentrates, has been found to be well tolerated and effective in clinical treatment of hemophilia A patients.
Adsorption↗
[Use of a biological glue in partial pulmonary excision surgery. Results of a controlled trial in 50 patients].
A controlled study concerning the surgical use of a fibrin glue was conducted in 50 patients undergoing partial pulmonary excision. In 25 of these patients, chosen at random, hemostasis and aerostasis of the fissural, and/or intersegmentary dissection planes were achieved by electrocoagulation, in the other 25 by the application of fibrin glue. The statistical study did not show any significant difference between the two groups in terms of the surgical indication, the type of excision and the associated surgical procedures (pleurectomy and parietectomy). No significant statistical difference was observed concerning the quality of aerostasis, the post-operative drainage, the persistance of residual collection or faulty reexpansion after removal of the latter, and the necessity for repeated drainage. The same applied to the length of post-operative hospital stay. This study seems to demonstrate that the surgical application of fibrin glue on the fissural and/or intersegmentary dissection planes is feasible but, as compared to electrocoagulation, does not significantly improve the quality of the surgical results for partial pulmonary excision; however its use could reduce the duration of post-operative drainage.
Adolescent↗
Re-evaluation of the role of azathioprine in the treatment of adult chronic idiopathic thrombocytopenic purpura: a report on 53 cases.
We treated 53 adults (mean age 54 years, range 17-89; 37 females and 16 males) with chronic idiopathic thrombocytopenic purpura (ITP) by azathioprine. All patients had received at least one form of therapy (including splenectomy in 40 patients) and had less than 50 x 10(9)/1 platelets. The duration of ITP before azathioprine was started ranged from 6 to 350 months (median 19). All patients initially received 150 mg/d of azathioprine. This was associated with a short initial course of prednisone (0.3-0.5 mg/kg d) in 10 of them, who were refractory to prednisone alone. 34 (64%) patients responded, including 24 (45%) complete remissions (CR), three (6%) partial remissions (PR) and seven (13%) minor responses (MR). Median time to achieve response was 4 months. 17 of the CR persisted after 7-182 months, 10 of them after discontinuation of azathioprine. Seven patients relapsed after 4-26 months, five of them after azathioprine was stopped or its dose was reduced. PR were short and the median duration of MR was 8 months. Overall, 21 patients (40%) had responses lasting 1 year or more and 17 (32%) lasting 2 years or more. Median duration of treatment was 18 months (range 3-84). Five patients died of bleeding while on treatment. No prognostic factors for response to azathioprine were found. Mild leucopenia was seen in seven patients and a moderate (x3) increase in transaminases in two patients. No opportunistic infections were seen and no malignancy has occurred since the onset of azathioprine. We conclude that azathioprine gives a relatively high incidence of durable responses and very limited side effects in chronic ITP, when splenectomy has failed or is contraindicated. This efficacy, in our experience, is superior to that obtained with other therapeutic approaches. As responses may be delayed, a course of azathioprine of 4 months is required before one can infer a failure to respond. In responding patients, however, the optimum duration of treatment remains to be established.
Adolescent↗
Biochemical and physical properties of a solvent-detergent-treated fibrin glue.
A fibrin glue preparation has been obtained from pooled human plasma using a procedure which includes a solvent-detergent (SD) treatment to inactivate lipid-enveloped viruses. The SD treatment inactivated greater than or equal to 5.5 log10 of HIV in less than 45 min, and greater than or equal to 5 log10 and greater than or equal to 6.5 log10 of VSV and Sindbis virus, respectively, in less than 2 h. The product was found to contain high quantities of fibrinogen (116 +/- 2.49 g/l; n = 12), factor XIII (35 +/- 2.88 U/ml) and von Willebrand factor (23 +/- 1.9 U/ml ristocetin cofactor activity), and relatively low levels of fibronectin (5.9 +/- 0.51 g/l). Plasminogen, the precursor of plasmin, which may play a negative role by decreasing the resistance of the fibrin clot, was at only 0.03 g/l. Cellulose acetate electrophoresis showed 95% gamma-proteins and 5% alpha-2-beta proteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions detected three main protein bands with apparent molecular weights of 65, 56 and 47 kilodaltons, probably corresponding to the alpha, beta, and gamma fibrinogen subunits. Other characteristics of the product included (1) high clottability of fibrinogen (over 85%); (2) absence of low molecular weight fibrin degradation products; (3) rapid solubilization at room temperature (less than 10 min); (4) high tensile strength (202 +/- 27 g/cm2 after 2 h of application), and (5) high elasticity of the fibrin clot. In addition, scanning electron microscopy revealed a highly organized structure showing tridimensional arrangement of the fibrin fibers. SD treated fibrin glue should efficiently replace autologous fibrinogen or cryoprecipitate preparations for surgical application.
Antiviral Agents↗
The role of danazol in the treatment of refractory idiopathic thrombocytopenic purpura. A report of 22 cases.
We treated 22 patients with refractory idiopathic autoimmune thrombocytopenic purpura (ITP) with Danazol (generic name). Median age was 57 (1 child aged 11, and 21 adults aged 18 to 77). Patients were refractory to or had contraindication to therapy by prednisone and splenectomy. Several patients had already received other treatments. All patients received Danazol at a daily dose of 600 mg/day for at least 2 months (except the child who received 400 mg/day), and other treatments for ITP were discontinued when Danazol was started. Two patients achieved complete remissions (CR), one partial remission (PR) and four had minor responses (MR). The remaining 15 patients had no response (NR). One of the complete responses lasted 34 months, but was dependent on daily maintenance doses of Danazol of 400 mg or more. One partial responder remained so after seven months, four months following the discontinuation of Danazol. All other responders relapsed within three months, while receiving Danazol 600 mg/day. The drug was generally well tolerated, with few side effects. Danazol, when used as a single drug in refractory ITP, therefore had limited benefit in our experience.
Adolescent↗
Translocation t(1;19)(q23;p13) in acute lymphoblastic leukemia. A report on six new cases and an unusual t(17;19)(q11;q13), with special reference to prognostic factors.
We report clinical, immunologic, and cytogenetic characteristics of six patients with a t(1;19)(q23;p13) that was balanced in one case and of the unbalanced type [-19,der(19)t(1;19)(q23;p13)] in the remaining five cases. Intracytoplasmic immunoglobulins (cIg) were positive in the three cases where they were found. We also report on another patient, with a t(17;19) involving 17q11 and probably 19q13 regions, although involvement of 19p13 could not be excluded. In this patient, cIg were also present, thus raising the issue of whether such a rearrangement could be a variant of t(1;19). Clinically, five patients belonged to the high-risk acute lymphoblastic leukemia (ALL) group, because of high leukocytosis, central nervous system (CNS) disease at presentation, or massive organomegaly. Cytologically, all cases were FAB type L1. Except for the two cases allografted in the first complete remission (CR) all patients relapsed, three of them within 13 months. Two CNS relapses were seen in spite of adequate CNS prophylaxis. ALL with t(1;19) appears to be a poor-risk ALL subgroup and probably requires a reinforcement of therapeutic modalities that might include, when possible, allografting at first CR.
Adolescent↗
Translocation t(10;17)(p13;q12) in two cases of acute nonlymphocytic leukemia with phagocytic activity of blasts. A new cytogenetic entity?
We report two cases of translocation t(10;17)(p13;q12) found in a series of 278 cytogenetically studied acute nonlymphocytic leukemia cases. Blast cells, in both cases, were undifferentiated and had phagocytic properties. These patients might represent cases of a new cytogenetic entity.
Adult↗
Properties of a highly purified human plasma factor IX:c therapeutic concentrate prepared by conventional chromatography.
We have characterized a highly purified (HP) factor IX concentrate intended for therapy of hemophilia B. The product has been prepared from pooled human plasma using a large-scale procedure combining three conventional chromatographic steps based on DEAE ion exchange and affinity on immobilized heparin. The specific activity of the product was 119 +/- 10 IU factor IX:c/mg protein (n = 15), corresponding to a purification factor of about 9,000. The concentrate was free of the vitamin K-dependent clotting factors II, VII and X and of proteins C and S. Most of the contaminants found in factor IX complex concentrate (PCC) were absent in this new product. High-molecular-weight kininogen, factors VIII, XI, XII or prekallikrein were not detected. There were no activated factors, such as factors IXa, and Xa, no thrombin and no phospholipids. Only two contaminants could be detected: C4 and inter-alpha-trypsin inhibitor (about 0.8 and 1.2 mg/1,000 IU factor IX:c, respectively). The purity of the product, as compared to PCC, was confirmed by sodium dodecylsulfate polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar-Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Thrombogenicity tests in rabbits revealed that the HP factor IX tested had a lower thrombogenic power than the PCC tested. The concentrate has been subjected to a 0.3% tri(n-butyl) phosphate-1% Tween 80 treatment for 6h at 25 degrees C during its production to reduce or eliminate the risk of transmission of plasma-borne lipid-enveloped viruses. These conditions inactivated more than 3.8 log10 of vesicular stomatitis virus and more than 4.3 log10 of sindbis virus within 1 and 2 h of treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Coagulation Factors↗
Cytogenetic studies in 30 patients with Burkitt's lymphoma or L3 acute lymphoblastic leukemia with special reference to additional chromosome abnormalities.
We performed cytogenetic analysis in 23 consecutive patients with Burkitt's ALL and 7 patients with Burkitt's lymphoma. Only one patient had a normal karyotype. Twenty-seven patients had a (8;14) translocation and 2 a (2;8) translocation. No (8;22) translocation was seen. In 12 patients (41%), the t(8;14) was the only chromosome rearrangement whereas in the 18 remaining cases (59%), the t(8;14) or t(2;8) was associated with other numerical or structural abnormalities. Chromosomes 1, 7 and 6 were rearranged in 10, 8, and 5 patients, respectively, usually in translocations, duplications, deletions (chromosome 6), or isochromosome of the long arm (chromosomes 1 or 7). The incidence of these additional rearrangements is discussed with regard to previously published reports and the chromosome localization of oncogenes.
Burkitt Lymphoma↗
Acute lymphocytic leukemia with 9p anomalies. A report of four additional cases and review of the literature.
Childhood acute lymphocytic leukemia (ALL) with partial deletion of the short arm of chromosome 9 (9p-), particularly in the p21-22 region, associated with bulky disease, has been regarded as a possible subgroup of ALL. We have reviewed clinical and cytologic data in 128 cases of ALL (childhood and adult). Four of them had 9p anomalies. Two patients had a deletion in the 9p21 region associated with another deletion (9p13----pter) in one case and with t(1;19)(q21;p13) in the second patient. A third patient had a t(9;14)(p21;q12) balanced translocation associated with 14q22----qter deletion; the last patient showed a t(5;9)(p14;q21) unbalanced translocation also associated with 14q deletion. All four patients had lymphomatous ALL, but immunophenotype was non-T, in the four cases, (non-T, non-B in two patients and common ALL in the two remaining cases). Acute lymphocytic leukemia with 9p anomalies appears relatively frequently and is usually associated with poor prognostic features (i.e., bulk disease and high leukocyte counts) but does not seem restricted to childhood and T-cell lineage.
Adolescent↗