Quantification of blood flow with dynamic MR imaging and presaturation bolus tracking

A technique is described for rapid imaging of blood flow and dynamic measurement of its velocity. The method is a combination of bolus tracking and low-flip-angle gradient-echo cine angiography. This method provides precise determination of velocity with high temporal resolution in a single measurement. Unlike what occurs in phase imaging techniques, flow is displayed directly, eliminating potential errors that result from non-flow-related sources of phase shifts. Manipulation of raw data sets is avoided. Results obtained from a flow phantom, healthy volunteers, and a patient with an aortic aneurysm demonstrate the capability of the technique to track flow at low and high velocities and to differentiate flowing blood from thrombus. Because of its conceptual simplicity, rapidity, and lack of susceptibility to extraneous phase shifts, this technique may prove ideal for in vivo flow measurement and evaluation of flow patterns.     

The effect of DDAVP on plasma levels of von Willebrand antigen II in normal individuals and patients with von Willebrand's disease

The infusion of 1-deamino-(8-D-arginine)-vasopressin (DDAVP) causes not only an elevation in factor VIII-related antigen (FVIIIR:Ag), but also a marked elevation of plasma von Willebrand antigen II (vWAgII). vWAgII reaches a peak concentration at 60 min and is elevated 3-8-fold over basal levels in normal individuals and individuals with type I, IIA, and IIB von Willebrand's disease. As the mechanism of hemostatic alteration brought about by DDAVP might be due to release of endothelial cell proteins, endothelial cell cultures were performed. The cultures demonstrated synthesis and secretion of vWAgII, as evidenced by the incorporation of 35S-methionine into the vWAgII molecule. Thus, vWAgII, like FVIIIR:Ag, is an endothelial cell protein.     

A comparison between activated protein C and des-1-41-light chain- activated protein C in reactions with type 1 plasminogen activator inhibitor

This study investigates the role of the gamma-carboxyglutamic acid (gla) containing domain of activated protein C in interactions with both platelet-derived and purified type 1 plasminogen activator inhibitor (PAI-1). The activity of human platelet PAI-1 was neutralized to the same extent by bovine activated protein C and bovine des-1-41- light chain-activated protein C. Both forms of activated protein C formed SDS-stable, divalent-cation independent complexes with platelet PAI-1, as demonstrated by immunoblotting using antibodies directed to either protein C or PAI-1. Since activated protein C neutralized PAI-1, the potential inhibition of the enzyme by PAI-1 was studied. Purified PAI-1 inhibited the amidolytic activity of bovine-activated protein C and bovine des-1-41-light chain-activated protein C with a k2 of 2.85 X 10(4) M-1 sec-1 for both proteins. These data suggest that the gla domain of activated protein C is not required for neutralization of PAI- 1 activity, for complex formation with PAI-1, or for inhibition of the amidolytic activity of activated protein C by PAI-1.     

The treatment of malignant histiocytosis

Twenty-four consecutive cases of malignant histiocytosis (MH) treated at Stanford Medical Center between 1973 and 1983 have been reviewed. Most patients presented with systemic symptoms (91%) and advanced disease (stage IV, 80%). Multiple organ involvement was common. In six cases, pathologic tissue was further characterized by frozen section immune histochemistry, using a panel of monoclonal antibodies known to react with monocytes and macrophages, as well as a variety of hematopoietic cells. One case expressed a mature monocyte/macrophage phenotype; three cases were considered null cell or primitive lesions; and two cases were identified as probable T cell lymphomas. Seven patients underwent splenectomy. Two patients died prior to any treatment. Twenty-two patients were treated with CHOP (cyclophosphamide, Adriamycin, vincristine, prednisone) +/- bleomycin (B), +/- midcycle high-dose methotrexate (HD-MTX) with leucovorin rescue. Seven patients received prophylactic intrathecal MTX. Of 22 evaluable patients, there was a 68% complete response rate (CR), a 23% partial response rate (PR), and a 9% no response rate (NR). Median duration of CR was 30+ months; median duration of PR was 2.4 months. Median survival for patients attaining a CR has not been reached v 3 months for the PR and NR groups. For all 24 patients, median survival was 2 years, with a 5-year actuarial survival of 40%. Multivariate analysis revealed that a platelet count less than 150,000 (P Cox = .005) and the dose of drug delivered (P Cox = .057) were the most important prognostic factors. Prophylactic intrathecal MTX therapy and splenectomy did not influence survival. Although MH is an aggressive disease with a poor prognosis, it is potentially curable. Systematic and aggressive treatment should further improve the outcome.     

BCL-6 expression during B-cell activation

Translocations involving the BCL-6 gene are common in the diffuse large cell subtype of non-Hodgkin's lymphoma. Invariably, the BCL-6 coding region is intact, but its 5' untranslated region is replaced with sequences from the translocation partner. The present study shows that BCL-6 expression is regulated in lymphocytes during mitogenic stimulation. Resting B and T lymphocytes contain high levels of BCL-6 mRNA. Stimulation of mouse B cells with anti-IgM or IgD antibodies, bacterial lipopolysaccharide, phorbol 12-myristate 13-acetate plus ionomycin, or CD40 ligand led to a five-fold to 35-fold decrease in BCL- 6 mRNA levels. Similar downregulation of BCL-6 mRNA was seen in human B cells stimulated with Staphylococcus aureus plus interleukin-2 or anti- IgM antibodies and in human T lymphocytes stimulated with phytohemagglutinin. BCL-6 mRNA levels began to decrease 8 to 16 hours after stimulation, before cells entered S phase. Although polyclonal activation of B cells in vitro invariably decreased BCL-6 MRNA expression, activated B cells from human germinal centers expressed BCL- 6 mRNA at levels comparable to the levels in resting B cells. Despite these similar mRNA levels, BCL-6 protein expression was threefold to 34- fold higher in germinal center B cells than in resting B cells, suggesting that BCL-6 protein levels are controlled by translational or posttranslational mechanisms. These observations suggest that the germinal center reaction provides unique activation signals to B cells that allow for continued, high-level BCL-6 expression.     

Evidence that fibrin alpha-chain RGDX sequences are not required for platelet adhesion in flowing whole blood

The role of the RGDX putative receptor-recognition sites, which are present on the alpha chains of fibrin, in promoting platelet adhesion has been examined in flowing whole blood using the rectangular perfusion chamber at wall shear rates of 340 and 1,600/s. Platelets adhered to a comparable extent to surfaces coated with native fibrin and surfaces coated with fragment X-fibrin, a product of limited fibrinolysis that lacks the RGDS sites normally present at positions 572 to 575 of the alpha chains. The strengths of these adhesive interactions were comparable based on the concentrations of the antiadhesive peptide D-RGDW required to block platelet deposition to native and fragment X-fibrin at both low and high wall shear rate. Blocking either or both RGDX sequences with peptide-specific monoclonal antibodies did not inhibit platelet deposition in perfusion experiments performed with normal blood at 340/s, indicating that neither RGD motif is required for adhesion. However, adhesion was partly inhibited by anti-RGDX antibodies when perfusions were performed with blood from an afibrinogenemic patient, suggesting the RGDX sequences may play a limited role in platelet deposition. Exposure of fibrin surfaces to plasminogen/tissue-type plasminogen activator did cause a time- dependent loss of adhesiveness, but this effect was only weakly correlated with proteolysis of the fibrin alpha chains. These observations provide evidence that neither RGDX sequence is required for platelets to adhere avidly to fibrin in flowing blood. These results further suggest that incomplete fibrinolysis yields a highly thrombogenic surface.     

A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity

Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease.     

ADA与EASD对2型糖尿病高血糖处理：治疗启动与评定的新共识方案

在不到一年时间由同一批专家代表ADA和EASD先后起草和发布了两次关于“2型糖尿病高血糖处理的共识声明”同时发表在2008年1月和12月的《DiabetesCare》和《Diabetologia》上。第一次共识声明内容主要围绕TZDs药物的安全性,本刊作了摘译转载（参阅《中国糖尿病杂志22008年第7期）。第二次修订的共识声明,关注点为降糖药的新分级,论据及观点比较清晰,故仍摘译供读者参考。     

Pulmonary lymphangitic carcinomatosis: CT and pathologic findings

The authors retrospectively reviewed the computed tomographic (CT) scans, biopsy specimens, autopsy results, and lobectomy specimens of 21 patients who had lymphangitic carcinomatosis. Ten-millimeter collimation CT scans were obtained from all patients, and selected 1.5-mm CT scans were obtained from ten patients. In five patients, the diagnosis was established with open lung biopsy, lobectomy, or autopsy; in nine, with bronchial biopsy or transbronchial biopsy; and in seven, with clinical and radiologic criteria. Certain characteristic findings on CT scans were evident: uneven thickening of bronchovascular bundles, thickening of isolated interstitial lines, and the presence of polygonal lines. These findings may be seen on CT scans even if the findings on chest radiographs are normal or nonspecific. The pathologic basis for these characteristic CT findings may relate to tumor thrombi in lymphatic vessels rather than edema and fibrosis, at least in the early stages of disease.