Molecular characterization of human factor XSan Antonio

Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio.     

Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients

Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis.     

Macro-optical trapping for sample confinement in light sheet microscopy

Light sheet microscopy is a powerful approach to construct three-dimensional images of large specimens with minimal photo-damage and photo-bleaching. To date, the specimens are usually mounted in agents such as agarose, potentially restricting the development of live samples, and also highly mobile specimens need to be anaesthetized before imaging. To overcome these problems, here we demonstrate an integrated light sheet microscope which solely uses optical forces to trap and hold the sample using a counter-propagating laser beam geometry. Specifically, tobacco plant cells and living Spirobranchus lamarcki larvae were successfully trapped and sectional images acquired. This novel approach has the potential to significantly expand the range of applications for light sheet imaging.OCIS codes: (110.0180) Microscopy, (110.0110) Imaging systems, (180.6900) Three-dimensional microscopy, (350.4855) Optical tweezers or optical manipulation     

Intérêt du coroscanner en urgence pour l’exclusion de la maladie coronaire chez les patients souffrant de douleur thoracique à risque faible ou intermédiaire

Purpose

To demonstrate the usefulness of the multislice computer tomography coronary angiography (CCTA) in patients with suspected acute chest pain without electrical changes or enzyme rise, and with low cardiovascular risk.

Patients and methods

Fifty-three patients at low or intermediate risk for coronary artery disease, who were admitted in the emergency department for an acute chest pain, and who underwent a CCTA, were included in the study. Results of the CCTA were classified as normal, non-obstructive stenosis (≤ 50% stenosis in diameter), obstructive stenosis (> 50% stenosis in diameter). The mortality was assessed during a 4-years follow-up period.

Results

Mean age was 61 years (36–86), 43% of patients were women. The CCTA was normal in 35 patients (66%), seven patients (13%) had non-obstructive stenosis and 11 (21%) had obstructive stenosis. In the group of normal CCTA, 8.5% of patients were admitted in cardiac intensive care unit, 57.1% in the non-obstructive stenosis and 90.9% in the group of obstructive stenosis. No deaths occurred during the 4-year follow up in the group of patients with normal CCTA.

Conclusion

This study confirms the negative predictive value of CCTA for the diagnosis of coronary artery disease and for further clinical events in patients at low or intermediate risk referred to emergency department for an acute chest pain.     

先天性肠闭锁166例临床分析

目的分析先天性肠闭锁病例的诊断及治疗,以提高治愈率及术后生活质量。方法回顾性分析166例先天性肠闭锁的临床资料。结果治愈142例,治愈率85.5%(142/166),其中包括18例二期手术治愈者;术中10例、术后8例放弃治疗;术后死亡6例。结论早期诊断和选择合理的术式是提高肠闭锁治愈率的关键,基础支持及手术技术改进能促进病情的恢复,改善预后。