A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein S deficiency type I.

In an attempt to explore the molecular mechanisms for protein S deficiency, a patient with such a deficiency was examined at the DNA, RNA and protein levels. Nucleotide analyses revealed that the proband, the mother and the grandmother had a G-->C substitution in the invariant AG dinucleotide at the splicing acceptor site of intron A/exon 2. This patient was heterozygous for this substitution and the mutant allele was inherited from the proband's mother and grandmother. Reverse transcription-polymerase chain reaction analysis demonstrated several kinds of splicing abnormalities such as exon skipping and cryptic splicing, in addition to correct splicing. Semiquantitation of mRNA for the protein S gene revealed that the amount of the proband's mRNA was reduced to 60% of normal. Thus, this mutation impaired the normal processing of mRNA for the protein S gene, resulting in the subject's severe protein S deficiency.

Antifibrinolytic therapy with tranexamic acid in cardiac operations.

To demonstrate its antifibrinolytic effects and establish an effective regimen of tranexamic acid for hemostasis, the authors measured alpha2-plasmin inhibitor-plasmin complexes, thrombin-antithrombin III complexes and postoperative blood loss in three groups undergoing different regimens during cardiac operations. Forty-six patients undergoing coronary artery bypass grafting or valve replacement were enrolled in this study. They were divided into three groups of drug administration. A bolus infusion of 50 mg/kg tranexamic acid was given to 17 patients at the end of cardiopulmonary bypass (control group) and to 14 patients at the beginning of cardiopulmonary bypass (group A). In addition to the same bolus infusion at the beginning of cardiopulmonary bypass as group A, a continuous infusion of 10 mg/kg per h, starting at the time of skin incision and maintained for 6 h after cardiopulmonary bypass was given to 15 patients (group B). The marked increase in alpha2-plasmin inhibitor-plasmin complexes at the end of cardiopulmonary bypass in the control group was significantly reduced in group A (P < 0.01) and a further reduction was observed in group B (P < 0.001). The difference in postoperative blood loss only reached significant levels between the control group and group B (P < 0.05). Although a significant increase in thrombin-antithrombin III complexes during cardiopulmonary bypass was similarly observed in all groups, no thromboembolic events occurred in any group, nor was any difference seen in graft patency. From the tranexamic acid therapy regimens tested in this study, a continuous infusion of 10 mg/kg per h starting at the time of skin incision to 6 h after cardiopulmonary bypass, with a bolus infusion of 50 mg/kg at the beginning of cardiopulmonary bypass, proved to be the most effective.

[A prospective study on the timing of discontinuation of aspirin before coronary artery bypass grafting].

The effects of the timing of discontinuation of aspirin before coronary artery bypass grafting (CABG) on postoperative blood loss and blood requirements were examined in 22 patients undergoing elective CABG, who were randomly assigned into two groups. In Group I (11 patients), aspirin was discontinued two days before the operation and in Group II (11 patients), aspirin was continued up to the operation. The other 40 patients, who did not take aspirin for at least seven days before the operation, served as a control Group. There were no differences in preoperative data including the platelet count and the hemoglobin concentration, nor in operative variables such as operation time, cardiopulmonary bypass duration and aortic crossclamp time among the groups. Although postoperative blood loss (six hours' loss; Group I 218 ml, Group II 183 ml and control Group 172 ml) and red blood cells transfusion requirements were not different among the groups, platelet concentrates transfusion was more frequently required in Group II (54.5%) as compared with control Group (7.5%) and Group I (9.1%). The difference between Group II and the control Group reached statistical significance (p < 0.01), but there was no significant difference between Group I and control Group. This fact suggests that preoperative two days' discontinuation of aspirin works as effectively as seven days' discontinuation.

[A catheter-guided insertion of Pacifico's venous cannula].

Direct caval cannulation using a Pecifico's cannula has become popular in open heart surgery. However, the cannulation is often difficult especially in pediatric cases because of the right-angled, blunt and large metal tip of the catheter. To resolve this problem, we introduced a catheter-guided insertion of the cannula using an intratracheal suction catheter (IZUMO Health, Nagano, Japan) of an appropriate size as a guiding catheter. With this technique, no special skills are necessary to establish direct caval cannulation.