No abstract

Familial hemophagocytic lymphohistiocytosis (FHL), also known as familial erythrophagocytic lymphohistiocytosis and familial histiocytic reticulosis, is a rare autosomal recessive disorder of early childhood characterized by excessive immune activation. Linkage of the disease gene to an approximately 7.8-cM region between markers D9S1867 and D9S1790 at 9q21.3-22 was identified by homozygosity mapping in four inbred FHL families of Pakistani descent with a combined maximum multipoint LOD score of 6.05. This is the first genetic locus to be described in FHL. However, homozygosity by descent across this interval could not be demonstrated in an additional affected kindred of Arab origin, whose maximum multipoint LOD score was -0.12. The combined sample revealed significant evidence for linkage to 9q markers (LOD score with heterogeneity, 5.00). Identification of the gene(s) involved in the pathogenesis of FHL will contribute to an understanding of the control of T-lymphocyte and macrophage activation, which is central to homeostasis in the immune system.

randomized study of computer-assisted oral anticoagulant dosage vs. medical staff dosage. J Thromb Haemost 2008; 6: 935-43.Summary. Background: Increased demand for oral anticoagulants is overwhelming facilities worldwide, resulting in increasing use of computer assistance. A multicenter clinical endpoint study has been performed to compare the safety and effectiveness of computer-assisted dosage with dosage by experienced medical staff at the same centers. Methods: A randomized study of dosage of two commercial computer-assisted dosage programs (PARMA 5 and DAWN AC) vs. manual dosage at 32 centers with an established interest in oral anticoagulation in 13 countries. The aim was to recruit a minimum of 16 000 patient-years randomized to medical staff or computer-assisted dosage. In total, 13 219 patients participated, 6503 patients being randomized to medical staff and 6716 to computerassisted dosage. The safety and effectiveness of computerassisted dosage were compared with those of medical staff dosage. Results: In total, 13 052 patients were recruited (18 617 patient-years). International Normalized Ratio (INR) tests numbered 193 890 with manual dosage and 193 424 with computer-assisted dosage. The number of clinical events with computer-assisted dosage was lower (P = 0.1), but in the 3209 patients with deep vein thrombosis/pulmonary embolism, they were reduced by 37 (24%, P = 0.001). Time in target INR range was significantly improved by computer assistance as compared with medical staff dosage at the majority of centers (P < 0.001). Conclusions: The safety and effectiveness of computer-assisted dosage has been demonstrated using two different marketed programs in comparison with experienced medical staff dosage at the centers with established interest in anticoagulation. Significant prevention of clinical events in patients with deep vein thrombosis/pulmonary embolism and the achievement of target INR in all clinical groups has been observed. The reliability and safety of other marketed computer-assisted dosage programs need to be established.

Summary. The success in achieving therapeutic international normalized ratio (INR) targets in the control of warfarin using a whole-blood point-of-care testing (POCT) monitor (CoaguChek) in a community clinic was compared with hospital laboratory coagulometer prothrombin time (PT) testing in a randomized crossover study. Forty-six patients were randomized into two groups. At each visit, capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer. In Group 1, for 6 months, dosage was based on the CoaguChek and for the second 6 months on the coagulometer. In the second group, the order was reversed. Dosages were determined using the dawn ac computer programme. Success was assessed by the percentage of time patients were maintained within the INR targets. Agreement between laboratory and monitor INR, and patient satisfaction were also assessed. Results with the POCT monitor compared well with the hospital coagulometer. Time in INR target range between the groups was similar, with 60AE9% on the POCT monitor and 59AE3% with the laboratory coagulometer in Group 1 and in Group 2, respectively, 64AE3% and 63AE4% with no significant difference in mean INR. An INR above 4AE0 gave some discrepant results. International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable. Patient questionnaires showed greater satisfaction with community POCT monitoring.

We have developed a competitor-based RT-PCR techniqueation with the FAB subtype M4Eo, and some groups using an which will detect and quantitate the CBF␤/MYH11 transcripts RT-PCR have found it exclusively in M4Eo, 4 while others have associated with inv(16)(q22;p13) and have used it to study found the abnormality in cases of M4 lacking abnormal presentation and follow-up samples of acute myeloid leueosinophils. 6 The sensitivity of the PCR test has allowed it to kaemia (AML). The levels of the leukaemia-specific transcripts be used to monitor residual disease following treatment, 4,6,7 are expressed as a ratio to a ubiquitously expressed mRNA species (Abl) which controls for RNA degradation. This techand PCR positivity has been found in patients in long-term nique has been applied to 75 consecutive patients presenting remission. 6,7 with either de novo AML or tMDS; 6/75 patients analysed wereIn a study of four patients with inversion (16) in patients in complete remission.