A novel mutation (Arg-->Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A.
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Arginine↗
Biomedical subjects
J M Bardin
Publications and source records attributed to J M Bardin.
Increased heparin cofactor II levels in women taking oral contraceptives.
Heparin cofactor II (HCII) is a thrombin inhibitor present in human plasma whose activity is enhanced by heparin. HCII exhibits important homologies with antithrombin III, the main heparin-enhanced thrombin inhibitor. Cases of recurrent thromboembolism have been recently reported in patients with HCII deficiency. Since the use of oral contraceptives (OC) is associated with an increased risk of thrombosis, the study of the plasma levels of HCII was undertaken in women taking contraceptive pills. Plasma HCII levels were found significantly higher in 62 women taking low-estrogen content OC (1.20 +/- 0.28 U/ml) than in 62 age matched women not taking OC (0.94 +/- 0.16 U/ml) or in 62 men (0.96 +/- 0.19 U/ml). Significant correlations between HCII and fibrinogen levels were reported in the three groups. From the pooled data of the two control groups (men and women not taking OC), the normal range for plasma HCII levels was defined to be between 0.60 and 1.30 U/ml (mean +/- 2 SD). Two cases of low HCII levels (less than 0.60 U/ml) were found in the control groups, but none in the group of women taking OC. It is concluded that the use of oral contraceptives is associated with a rise in HCII levels and that the screening for HCII deficiency has to be performed at distance of any OC therapy.
Adolescent↗
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↗
[Preparation of maternal platelets collected by separator for use in fetal transfusion in a case of alloimmunization by anti-PLA1].
In one case of fetal thrombocytopenia due to maternal immunization against PLA1 fetal platelet antigen, maternal platelets were collected by automated plasmapheresis. The platelets were collected 24 hours before fetal transfusion at 28, 29, 31 and 36 weeks of gestation. The maternal platelets were irradiated and concentrated in a small volume (7.10(10) to 1,4.10(11) plts in less than 20 ml maternal plasma) a few hours before transfusion. When prepared as described, maximal and irreversible platelet aggregation is obtained with 20 microM of ADP and the pH is over 6, 5-6 hours after concentration. The amounts of transfused platelets were determined to increase theoretically fetal platelet counts over 200,000 plts/mm3. The fetal platelet counts, determined immediately after transfusion, showed an increase of 100,000 plts/mm3. Prenatal fetal transfusion of maternal platelets is available to avoid fetal bleeding during delivery, and during the early neonatal period.
Adult↗
[Safety of hepatitis B vaccine with regard to the transmission of HIV].
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Acquired Immunodeficiency Syndrome↗
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↗
[Anti-LAV/HTLV III antibodies in wives of seropositive hemophilic patients].
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Acquired Immunodeficiency Syndrome↗
De novo mutation in hemophilia A established by DNA haplotype analysis and precluding prenatal diagnosis.
In a family with a single case of hemophilia A genetic counselling was requested by the pregnant aunt of the propositus. The haplotypes generated by two extra-genic RFLPs, at DXS52 (St14/Taq1) and DXS15 (DX13/BglII), and one intragenic RFLP in F8C (647/BclI) indicated that: she was not a carrier; the case of hemophilia resulted from a de novo mutation in a grandfather's gamete.
DNA↗
[Prenatal diagnosis of hemophilia A by analysis of DNA].
Early ante-natal diagnosis of haemophilia A and the detection of female carriers is now possible in some cases by analysis of DNA. The diagnosis may be established with a 100 p. 100 reliability in subjects with large deletion by direct analysis, and in 40 p. 100 of haemophiliac families by linkage studies with the intra-genic polymorphism revealed by the restriction enzyme BcII. Intensive research indicates that this percentage will increase in the near future. In the meantime, indicative studies are possible in other families. They consist in studying extra-genic restriction polymorphism. Over 90 p. 100 of families with haemophilia A may benefit from these studies using the probes currently available. Recombination, although not yet described, remains possible, and therefore ante-natal diagnoses made by the extra-genic probe should be controlled by foetal blood sampling at the 20th week of pregnancy.
DNA↗
[2 cases of AIDS in patients with hemophilia A].
The authors report the first two cases of lethal AIDS in haemophilia A in France. One French case of AIDS in haemophilia B has already been reported. The diagnosis was based on the observation of opportunist infections associated with severe depression of cell-mediated immunity in both cases. The possibility of active transmission of the LAV retrovirus by factor VII concentrate is discussed. This raises the problem of the signification of anti-LAV antibodies in haemophiliac patients and the control of products used for the treatment of haemophilia.
Acquired Immunodeficiency Syndrome↗
Decrease of [14C]2-deoxyglucose uptake at the intracerebellar nuclei during cerebellar cortex stimulation.
The effect of electrical stimulation of the cerebellar cortex at 10-30 c/s on metabolism in the intracerebellar nuclei has been studied using the [14C]2-deoxyglucose method. The experiments, performed on anesthetized or immobilized animals did not produce any detectable changes in the radioautographic labeling of the intracerebellar nuclei compared with controls. Experiments were also performed in animals pretreated with 3-acetylpyridine neurotoxin which selectively destroys the inferior olive and produces an intense labeling of the intracerebellar nuclei. Less marking was observed in restricted regions of the intracerebellar nuclei receiving the axon terminals of the stimulated Purkinje cells if the experiments were done within the first few hours. Following 3-acetylpyridine intoxication, in this early phase, destruction of the inferior olivary cell bodies occurs, but the climbing fibers remain intact. At 2 days or more following 3-acetylpyridine, changes in marking with stimulation could no longer be obtained. The finding is interpreted as being due to an actual reduction of the Purkinje cell activity upon stimulation of the cerebellar cortex, leading to a reduction of the metabolic activity at their presynaptic terminals.
Animals↗
Cerebellar output regulation by the climbing and mossy fibers with and without the inferior olive.
The activity of the olivocerebellar complex and the structures related in series with it have been studied using the complementary action of harmaline and 3-acetylpyridine to isolate the two principal inputs to the cerebellar Purkinje cells. The activities of the various nuclei as well as the entire brain have been simultaneously monitored using the [14C]2-deoxy-glucose method under the various combined effects of the pharmacological agents. (1) Tremogenic doses of harmaline increased the frequency of discharge in selected parts of the olivocerebellar system, increasing climbing fiber input and reducing Purkinje cell simple spike discharges in corresponding parts of the cerebellar cortex. The metabolic activity increased in the inferior olive and in the red nucleus. The results are interpreted as a net reduction of Purkinje cell inhibition on their target neurons, leading to a facilitatory cerebellar output. (2) Systemic injection of neurotoxic doses of 3-acetylpyridine selectively produced total degeneration of the neurons in the inferior olive, resulting in the suppression of complex spikes and a net increase in simple spike output from the Purkinje cells. The metabolic consequences were a reduction or absence in the inferior olive, decrease in the red nucleus, and increases in the Purkinje cell target neuron regions, including the intracerebellar and vestibular nuclei. The study of long survival times following the neurotoxic treatment revealed a transient metabolic marking of the inferior olive during the active glial processes accompanying the degeneration. In other parts the radioautographic changes caused by the destruction of the inferior olive persisted for about 1 month after the administration of the drug. (3) Tremogenic doses of harmaline were given to rats at different times following treatment with 3-acetylpyridine. It was demonstrated that: (a) intoxication of the inferior olive started within the second hour after 3-acetylpyridine administration, corresponding to the time at which the metabolic response to harmaline was also abolished; and (b) the increased metabolic activity produced by harmaline in the olivocerebellar complex was a consequence of an increased activity of the neurons of the inferior olive rather than a direct pharmacological effect of the drug. (4) Partial lesions of the inferior olive led to increased metabolic activity of those parts of the intracerebellar nuclei topographically related to the destroyed parts of the inferior olive. (5) In 3-acetylpyridine-treated animals, local ablation as well as local inactivation of the cerebellar cortex produced localized suppression of the intense labeling in the intracerebellar nuclei obtained in these animals. Since these regions receive synapses which are normally inhibitory, suppression of labeling clearly supports the hypothesis that regional marking may very well be produced by the activity of the presynaptic terminals themselves...
Animals↗
[Cerebellar disfacilitation after pharmacological destruction of the inferior olive].
The total selective destruction of the inferior olive by 3-acetylpyridine produces a marked increase in the metabolic activity at the intracerebellar nuclei. This increase is locally suppressed by partial ablation or local inactivation of the corresponding regions in the cerebellar cortex, suggesting its localization in the intranuclear presynaptic terminals of the Purkinje cells. In a second series of experiments, it is demonstrated that Purkinje cells of the cerebellar cortex deprived of their climbing fibers and therefore of their complex spikes by destruction of the inferior olive, increase their firing frequency of simple spikes. As a consequence, there is a decreased frequency of discharge of their target neurones in the intracerebellar nuclei; the net result of suppression of the inferior olive is thus an increased cortico-nuclear inhibitory effect.
Animals↗