Patterns of use of antithrombotic therapy and quality of anticoagulation among patients with non-valvular atrial fibrillation in clinical practice

We conducted a retrospective cohort study of thromboprophylaxis rates and the quality of anticoagulation control among patients with atrial fibrillation (AF) using a large, geographically diverse database of electronic medical records. The study population consisted of 13,709 AF patients treated in US outpatient physician practices. Approximately two-thirds were prescribed warfarin alone or in combination with another drug. Older patients, males, and those with congestive heart failure (CHF) or prior stroke were more likely to receive antithrombotic therapy. Among 6454 patients treated with warfarin who had at least two valid prothrombin time/international normalised ratio test results, approximately half of study days were spent in target range. Female sex, CHF and residence in the Northeast were associated with more time out of range. Our study confirms that, in routine medical practice, warfarin is not prescribed for substantial numbers of eligible patients, and anticoagulation control with warfarin is suboptimal for many of those at risk for thromboembolism.     

Platelet-bound complement (C3) in immune thrombocytopenia

The fixation of complement to the circulating platelet in immune thrombocytopenia was detected by measurement of one of the complement components, C3, on the surface of platelets from patients with idiopathic thrombocytopenic purpura (ITP) and systemic lupus erythematosus (SLE) using the anti-C3 consumption assay. The surface IgG was determined simultaneously using the previously described anti- IgG consumption assay. Washed platelets from normal controls had 3.5 fg (10(-15) g) of C3, or about 11,000 molecules, per platelet, an amount comparable to the IgG (4.1 FG, or 15,000 molecules, per platelet). For most patients with ITP both C3 and IgG were increased on the platelet surface, although for 5 of 16 patients only IgG was increased. Two patients with SLE and thrombocytopenia had an increase in both C3 and Ig, six patients with SLE who were not thrombocytopenic had normal amounts of membrane-bound C3 and IgG. In 5 patients, 3 with ITP and 2 with collagen vascular disease, both surface immunoproteins decreased with successful treatment of the thrombocytopenia.     

Interleukin 2-activated killer cells in patients following transplants of soybean lectin-separated and E rosette-depleted bone marrow

During the early period following bone marrow transplantation before the immune system has reached full functional maturity, unprimed, nonspecific lytic systems may play a critical role as antiviral or antitumor effectors. The reconstitution of cells with this potential is of particular importance in recipients of bone marrow that has been depleted of mature T lymphocytes to prevent graft v host disease (GVHD). We examined the recovery of natural killer (NK) cells and interleukin 2 (IL 2)-augmented lymphokine-activated killer cells (LAK) in 48 patients at various intervals following transplantation of bone marrow depleted of mature cellular elements by treatment with soybean agglutinin and sheep RBCs (SBA-E- BMT). We found normal levels of both NK and LAK activity as early as 3 weeks following SBA-E- BMT. When compared with cells from controls, NK and LAK precursors from transplant recipients appeared to be activated in vivo in that freshly isolated peripheral blood mononuclear cells (PBMCs) from patients had an elevated cytolytic activity toward NK-insensitive targets and a more rapid response to activation by IL 2. In patients as well as controls, both LAK precursors and LAK effectors lacked antigens present on mature T lymphocytes (CD3, CD4, or CD8) but expressed antigens present on NK cells (CD2, CD16, and NKH1A). The LAK cells did not lyse either donor or host peripheral blood T cell targets. The activity of NK effectors but not LAK precursors survived the in vivo total body irradiation used for pretransplant conditioning in three patients studied. LAK precursors could be demonstrated as early as 18 days following transplant at a time when the bone marrow contained primarily donor- derived cells. Little or no LAK activity could be generated from cells of the SBA-E- BM graft itself, suggesting that LAK precursors differentiate rapidly from more primitive progenitors in the marrow graft. Thus, our data indicate that the NK and LAK lytic systems are among the earliest activities to recover during immune reconstitution following T cell-depleted BMTs.     

Gastric operations and glucose homeostasis. II. glucagon and secretin.

Alimentary hyperglycemia in patients who have undergone gastric operations may be due, in part, to altered intestinal signals for glucose disposition. We measured glucose, immunoreactive insulin (IRI) pancreatic glucagon (IRG), and glucagon-like immunoreactivity (GLI) after oral glucose in patients with prior antrectomy or vagotomy and pyloroplasty and in normal individuals. All subjects had normal assimilation coefficients for intravenous glucose, which suggests that the responsiveness of the pancreatic beta-cells had not been altered by the surgical procedures. The early hyperglycemic response to oral glucose and the associated elevation of plasma GLI were much greater and the IRI levels slightly higher in both experimental groups in comparison to normal subjects. A decrease in the level of IRG, albeit not statistically significant, was noted in all groups after the ingestion of glucose. In gastrectomy patients, secretin infusion during repeated oral glucose tolerance tests partially corrected the hyperglycemia and lowered plasma GLI and IRI levels. The responses of the vagotomy and pyloroplasty patients and of the normal subjects were not altered by secretin infusion. We conclude that the intolerance or oral glucose after gastric surgery may be related to elevated GLI levels, and that the beneficial effect of secretin may be due to its ability to decrease these levels.