Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Clot Strength as Measured by Thrombelastography Correlates with Platelet Reactivity in Stroke Patients.

OBJECTIVE: Platelet reactivity may be important in the management of patients with stroke. However, degree of platelet reactivity has not been correlated with Thrombelastography (TEG(®)) parameters in stroke. We sought to detect a correlation between TEG(®) values and clot platelet reactivity in ex vivo clots of stroke patients. METHODS: We collected venous blood from 40 patients with stroke. TEG(®) measurements were carried out and residual clots were fixed in 10% formalin immediately following completion of TEG(®). The formalin specimens were embedded in paraffin blocks, cut at 4 micrometers, and stained with CD 61 (immunohistochemical stain used to detect platelets) with appropriate controls. Under light microscopy, three pathologists blinded to TEG(®) results independently graded CD61 intensity (how aggregated/intense the CD61 stained) into a low and high group, as a proposed measurement representing the platelet reactivity of the clot. We compared pre-tPA-TEG(®) values among groups with different CD 61 intensities. RESULTS: After adjusting for confounding factors, we found statistically significant correlation between CD61 staining and several TEG(®) parameters (Delta and CD61 staining intensity (p=0.047); Angle and CD61 staining intensity grade (p=0.04); and G and CD61 staining intensity grade (p=0.04)). CONCLUSIONS: Clot strength on TEG(®) as measured by Delta, Angle, and G correlates with a clot with greater platelet reactivity

Thrombelastography does not predict clinical response to rtPA for acute ischemic stroke.

Thrombelastography (TEG) measures coagulation in venous blood. We hypothesized that TEG, by reflecting clot subtype and ex vivo fibrinolysis, might predict fibrinolytic response to tPA as reflected by rapid clinical improvement or hemorrhagic transformation of the infarct. 171 acute ischemic stroke patients treated with tPA were prospectively enrolled. Venous blood for TEG was drawn before and 10 min after tPA bolus. We measured rapid clinical improvement (RCI = 8 point improvement on NIHSS or total NIHSS of 0, 1 at 36 h), Hemorrhagic transformation (HT = any blood on imaging within 36 h), and hyperdense middle cerebral artery sign (HDMCA = biomarker for erythrocyte-rich clot). Multivariable regression models compared TEG parameters after adjusting for potential confounders. No differences in pre- or post-tPA TEG were found between patients with or without RCI. Also, there was no correlation between TEG and HDMCA. Clotting was slightly prolonged in patients with HT (p = 0.046). We failed to find a robust association between TEG and clinical response to tPA. It is likely that arterial clot lysis is determined by factors unrelated to coagulation status as measured by TEG in the venous circulation. It is unlikely that TEG will be useful to predict clinical response to tPA, but may help predict bleeding

Iodinated contrast does not alter clotting dynamics in acute ischemic stroke as measured by thromboelastography.

BACKGROUND AND PURPOSE: Iodinated contrast agents used for computed tomography angiography (CTA) may alter fibrin fiber characteristics and decrease fibrinolysis by tissue plasminogen activator (tPA). Thromboelastography (TEG) measures the dynamics of coagulation and correlates with thrombolysis in acute ischemic stroke patients. We hypothesized that receiving CTA before tPA will not impair thrombolysis as measured by TEG. METHODS: Acute ischemic stroke patients receiving 0.9 mg/kg tPA RESULTS: Of 136 acute ischemic stroke patients who received tPA, 47 had CTA before tPA bolus, and 42 had either CTA after tPA and post-tPA TEG draw or no CTA (noncontrast group). Median change in clot lysis (LY30) after tPA was 95.3% in the contrast group versus 95.0% in the noncontrast group (P=0.74). Thus, tPA-induced thrombolysis did not differ between contrast and noncontrast groups. Additionally, there was no effect of contrast on any pre-tPA TEG value. CONCLUSIONS: Our data do not support an effect of iodinated contrast agents on clot formation or tPA activity