Primary care anticoagulant clinic management using computerized decision support and near patient International Normalized Ratio (INR) testing: routine data from a practice nurse-led clinic

BACKGROUND: Increasing indications for warfarin therapy has led to increased pressure on primary care to undertake therapeutic monitoring. OBJECTIVE: This study evaluates a primary care model of oral anticoagulation monitoring which utilises computerized decision support (CDSS) and near patient testing (NPT) within a practice nurse-led clinic. Whilst this has been shown to be a successful model under trial conditions, this paper reports the first data from a long-standing clinic, outside a formal study. METHOD: A prospective evaluation of therapeutic and clinical control of all patients taking warfarin within one inner city general practice. Data were collected via CDSS. RESULTS: 29 patients were seen in 208 appointments. The mean percentage of patients within therapeutic range was 72%. The costs to the practice were pound sterling 1751. The costs the practice would have incurred had these patients been seen at the hospital with the same frequency would have been pound sterling 2290. CONCLUSIONS: The use of CDSS and NPT for nurse-delivered oral anticoagulation monitoring could enable the safe transfer of the majority of patients from secondary to primary care. Funding mechanisms to support the transfer of costs will be essential for most practices, as will be the maintenance of adequate staff training and quality assurance.      

Xenogeneic expression of human stem cell factor in transgenic mice mimics codominant c-kit mutations

Mutations of c-kit, which encodes a transmembrane receptor tyrosine kinase, have been identified in mice by abnormal coat color, anemia, and germ cell defects. Mice heterozygous for mutations of c-kit have a white forehead blaze and a white ventral spot, leading these mutants to be termed dominant White spotting (W). We have previously demonstrated that the membrane-associated isoform of human stem cell factor (hSCF220, the ligand for c-kit) is inefficiently processed in murine stromal cell transfectants. Thus, in murine cell lines analyzed in vitro, hSCF220 transfectants present SCF as a membrane restricted protein in contrast to the murine SCF220 cDNA protein product, which is slowly cleaved and secreted. We show here that transgenic mice expressing the human SCF220 isoform in vivo display a phenotype indistinguishable from some alleles of W. Specifically, hSCF220- expressing transgenic mice display a prominent forehead blaze and a white ventral spot. Generations of doubly heterozygous animals that carry both a mutated c-kit allele and the hSCF220 transgene display a more severe coat color abnormality. This phenotype appears to be due to occupancy of murine c-kit by human SCF and diminished cell surface expression of endogenous murine SCF. Normal signaling events that lead to cell survival or proliferation appear to be disrupted in vivo in these transgenic mice.     

Epstein-Barr virus and familial Hodgkin's disease

Several studies suggest that the Epstein-Barr virus (EBV) is etiologically linked to Hodgkin's disease (HD). This study was undertaken to examine the role of EBV in familial HD (FHD). Among 60 FHD patients from 27 families with two or more cases per family, we tested available paraffinized tumor tissues from 46 cases by in situ hybridization for EBV-encoded RNA (EBER1) expression. Thirteen of 46 FHD patients (28%) had EBER1 expressed in the Reed-Sternberg cells. Concordance rate of EBV positivity was evaluated among 34 first-degree related pairs from 17 families for which both cases had available paraffinized tumor tissues. Only two of 17 pairs were concordant for EBER1 positivity. There was no excess of positive concordance (P = .18). Serologically, FHD patients had higher geometric mean antibody titers (GMTs) to the viral capsid antigen (VCA) and early antigen D (EA- D). There was no difference in seroprevalence between patients and control groups, nor was there concordance in elevated serology among 15 pairs of first-degree related FHD cases. Young adult unaffected family members (UFM) may not react to EBV in the same way as the general population as evidenced by the lower titer of VCA, although not statistically significant, and significantly lower titers of EA-D, compared with age-matched controls. While EBV might have some role in a subset of HD, lack of concordance of EBER1 expression and EBV serology among the FHD cases in the same family suggest that EBV does not play an important role in FHD.     

海南省HIV血清学检测报告

本文报告从海南省十一个HIV监测哨点采集的19653份血清标本中,发现了5例HIV抗体阳性者。这5例都是从泰国探亲回国时检测证实为Ⅰ型艾滋病病毒感染者的,表明我省近期内HIV传播的主要威胁途径为境外感染。     

Risk of leukemic transformation in PV and ET patients

Despite a prolonged survival of around 15 years linked to a prolonged complete remission induced by myelosuppression, myeloproliferative syndromes such as polycythemia vera (PV) and essential thrombosis (ET) remain at risk of lethal adverse affects such as thrombotic events and acute transformation. The major risk at diagnosis, in the absence of treatment, is essentially thrombosis. Different therapeutic trials have shown the necessity to maintain circulating blood cells (RBC and platelets counts) near normal levels to avoid thrombosis. Phlebotomies alone in PV lead in the long run to metaplasia and increased platelet counts and should only be kept for emergency cell count reduction. Myelosuppression is thus until recently the most widely accepted effective alternative. However, the effects of long term chronic administration of myelosuppresive agents needs to be analyzed and monitored as the biological changes which appear during the course of these diseases linked or not to the intrinsic clonal haematopoietic abnormality may lead to malignant transformation. Thus, alternative therapies need to be evaluated and predisposition factors taken in account.     

Platelet and Fibrinogen Sequestration

1. Small amounts of thromboplastin intravenously cause platelet sequestration. This is followed by fibrinogen sequestration. Large doses of intravenously administered thromboplastin lead to irreversible destruction or utilization of platelets and fibrinogen.

2. The following theories are advanced: (a) This platelet sequestration maybe due to platelet clumping caused by coagulation occurring on the plateletsurface. Surface coagulation may be initiated by the action of thromboplastinor thrombin on the plasma proteins and calcium adsorbed on the plateletsurface. The platelet clumps may be filtered out in the sinusoidal spaces of thebody, especially in liver and spleen. (b) The coagulation on the platelet surface may lead to partial polymerization of the fibrinogen molecule. (c) As longas this polymerization is reversible, the entire process remains reversible. Whenpolymerization proceeds far enough so as to become irreversible, the plateletsand fibrinogen can no longer return to the circulation. (d) This same mechanism may explain other examples of platelet sequestration.