[Sodium valproate in the treatment of choreoathetosis].
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Biomedical subjects
Publications and source records attributed to R Castillo.
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Changes in the morphology of human platelets induced by ristocetin in platelet-rich plasma (PRP) have been analysed at the ultrastructural level by means of a tannic acid procedure. Studies were also undertaken to measure the release of serotonin. Modifications of the aggregation tests induced by apyrase, a monoclonal antibody (Mab) to GPIIb/IIIa and by EDTA were also investigated. Transmission electron microscopy revealed that ristocetin precipitated adhesive proteins on the platelet membrane. An electron-dense deposit was seen within 20 s after ristocetin was added. When experiments were carried out in the aggregometer cuvette during stirring, groups of platelets became activated, changed their shape, and finally aggregated releasing part of their contents. The morphology of aggregates did not differ from those formed in the presence of ADP. Aggregation studies demonstrated that a Mab to GPIIb/IIIa modified the extent and the rate of the aggregation curve when RIPA was performed in citrated platelet-rich plasma (c-PRP), while apyrase modifies the extent, but not the slope, of the curve. Neither the antibody nor apyrase modified RIPA when it was performed in PRP obtained in the presence of EDTA. All this evidence suggests that RIPA in c-PRP, besides reflecting the interaction of GPIb with vWF, may also test other mechanisms of the platelet function including: assembly of GPIIb/IIIa complex, interaction of fibrinogen with this glycoprotein complex, and possibly the release reaction.
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We have studied the effect of ticlopidine on platelet function. This effect was assessed by aggregation studies and by the Baumgartner perfusion system as an ex vivo approach to study modifications in the interaction of platelets with vascular subendothelium. Platelets from volunteers, that were given 250 mg of ticlopidine twice a day showed a significantly decreased aggregation of platelets induced by several agonists. In the perfusion studies a marked reduction in the parameters that measure platelet interaction with subendothelium was also observed. The decrease in thrombus formation, and the diminished size of platelet aggregates, clearly indicated that ticlopidine impaired platelet-platelet interaction in this experimental flowing system. Our results suggest that ticlopidine is a potent inhibitor of platelet function and that its antiplatelet activity might be related to the mechanisms that regulate the interaction between platelets at the membrane level.
Even though it is generally held that cryoprecipitate and fraction I-O correct the prolonged bleeding time (BT) in patients with von Willebrand disease (VWD), perusal of reported data indicates that the correction is usually short-lasting and often partial. We decided to do a controlled study of the relationship between the multimeric structure of von Willebrand factor (VWF) and the BT in five patients with severe (type III) VWD after infusion of three plasma concentrates ("wet" cryoprecipitate, lyophilized cryoprecipitate, and fraction I-O) given in random order. The dosage of concentrates was tailored from in vitro measurements to achieve post-infusion levels of ristocetin cofactor above the lower normal limit (50 U/dL) for at least 3 hours. The postinfusion BT became transiently normal in only two of five patients treated with wet cryoprecipitate, whereas it remained prolonged in all five patients treated with lyophilized cryoprecipitate or fraction I-O. For all the concentrates, the proportion of large VWF multimers calculated by scanning the electrophoretic gels were the same as those for normal standard plasmas. An intact multimeric structure was recovered in postinfusion plasmas of patients treated with wet cryoprecipitate, whereas there was a postinfusion loss of large multimers after lyophilized cryoprecipitate and fraction I-O. These findings indicate that the attainment of a normal BT is the exception rather than the rule after the infusion of three plasma fractions used in the treatment of severe VWD, and that an intact multimeric structure in concentrates and postinfusion plasmas is necessary but not sufficient to sustain a normal BT.
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Using the Baumgartner perfusion technique, marked sex-related differences in the extent of platelet-subendothelium interaction and in the effect of aspirin (ASA) have been observed. The administration of ASA (150 mg daily for 15 days) to two groups of healthy volunteers, one composed of males and the other of females, proved to block the generation of TXB2 in both cases. The basic pattern of platelet subendothelium interaction, however, was found to be markedly different in both groups studied. In men, aspirin treatment induced a significant reduction in the percentage of platelet thrombi, whereas in women, post ASA values remained at the same level as in control experiments. These results show that in the Baumgartner perfusion system women display a less thrombogenic tendency than men and that 150 mg of ASA administered daily are effective in reducing the extent of platelet-subendothelium interaction in the male group but not in the female group. These findings could explain the absence of benefit observed for women in clinical trials with aspirin.
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Six different protocols were employed in 710 plateletpheresis employing Haemonetics 30, Fenwal CS-3000, IBM 2997 dual stage channel, IBM 2997 single-stage channel, and Haemonetics V-50 "surge pump" method. When Haemonetics 30 and IBM 2997 single-stage channel procedures were used, 5.4 to 5.9 X 10(11) platelets were collected with significant leukocyte contamination (10.8 to 11.6 X 10(9)). With Fenwal CS-3000, dual-stage channel of IBM 2997 and Haemonetics V-50 "surge pump" there was less leukocyte contamination in concentrates (0.3 to 0.9 X 10(9)) as well as a lower platelet yield (3.4 to 4.3 X 10(11)). No difference in yield was observed when plateletpheresis was performed with ACD-A or ACD-B employing the single-stage channel of IBM 2997. Paresthesias was the most frequently seen side effect in donors, with a higher incidence when using ACD-A and IBM 2997.