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The various superstructure phases that occur with the anion-deficient compositions of binary oxides MO2 − x with the fluorite structure as parent are explored here in terms of the original `coordination defect' (or CD) concept in which each vacant oxygen site, □, is `coordinated' by six O atoms thereby creating the octahedral `structure-determining' entity [ M3.5□O6]. It emerges that the structure and composition of each anion-deficient (polymorph) phase can be described in terms of crystallographic `motifs' which comprise sets of parallel coplanar polygons based on ½〈210〉F and ½〈111〉F CD linkages. [ABSTRACT FROM AUTHOR]

Summary. Defective hemostasis in haemophilia patients with FVIII inhibitors results in a dramatic decrease in thrombin generation forming unstable fibrin clots that are susceptible to fibrinolyisis. In this study we tested whether the combination of plasma derived activated prothrombin complex concentrate (pd-aPCC) with tranexamic acid (TXA) may improve fibrin clot stability in FVIII inhibitor plasma. A microplate assay for clot lysis time was used to assess clot stability in FVIII inhibitor plasma. The effect of pd-aPCC on clot stability was first tested using the commercial FVIII inhibitor plasma. TXA (5 ∼ 10 mg mL−1) increased clot lysis time, but pd-aPCC (0.25 ∼ 1.0 U mL−1) had no effect on it. The combination of pd-aPCC and TXA significantly increased clot lysis time compared with TXA alone. The effect appeared to be limited to fibrin clot resistance to fibrinolysis, as TXA was found to have no effect on thrombin generation induced by pd-aPCC. The effect of pd-aPCC and TXA on clot stability was then tested and verified in plasma samples from ten patients with severe haemophilia A and inhibitors. The combination of TXA (10 mg mL−1) and pd-aPCC (0.5 U mL−1) significantly increased clot lysis time compared to TXA alone. Our results suggest that the combination of pd-aPCC with TXA improves clot stability in FVIII inhibitor plasma without additional increases in thrombin generation. [ABSTRACT FROM AUTHOR]

Neoplastic cells from 49 patients with B cell chronic lymphocytic leukaemia (B-CLL) were studied and compared with normal peripheral and tonsillar B cells using CD21 monoclonal antibodies. Membrane expression of CR2 was quantified by calibrated flow cytometry and by binding analysis with radiolabelled antibody. Both assays indicate that B-CLL cells express only 30% of the CR2 found on normal B cells. These findings are further evidence of the aberrant phenotype of B-CLL cells. [ABSTRACT FROM AUTHOR]

Rat T-cell populations were analysed for their surface expression of CD4, CD8 and class II MHC antigens using monoclonal antibodies (McAbs) W3/25, Ox8 and Ox6 in immunofluorescence and immunoenzyme cytochemistry. Resting T cells expressed either CD4 (W3/25) or CD8 (Ox8) molecules, but not both, and did not express class II MHC antigens. In contrast, when purified T cells were stimulated by Con A or by alloantigens in a mixed lymphocyte reaction (MLR), over 60% of the cells expressed class II MHC antigens after 48-72 hr. The expression of class II MHC antigens by the T-cell blasts was transient and no longer evident after 96 hr of activation. In addition, T cells activated by either alloantigen or lectin expressed CD4 (W3/25) and CD8 (Ox8) molecules simultaneously: 30% of cells activated in MLR and 50% of Con A-activated cells expressed both markers within 48 hr of activation. The overlapping of the CD4- and CD8-positive subpopulations within the T-cell population was inferred from the results of staining for each marker separately and confirmed using a double-immunoenzyme staining method. [ABSTRACT FROM AUTHOR]

We consider the problem of locating a mobile object (user) in the cellular communication system on the basis of the triangulation method and the Gaussian multipath-channel model under urban conditions of signal propagation. The probability density function of the maximum likelihood estimate of Cartesian coordinates of the user is found if two or three base stations arbitrarily located with respect to one another are used. It is shown that the user-locating error depends on the distance between the base stations, mutual location of the user and the base stations, and the variance of the user-bearing estimation error for each base station. In this case, using the third base station significantly improves the user-locating accuracy. [ABSTRACT FROM AUTHOR]

The article presents a study on the prevalence of thrombophilia and hyperhomocysteinaemia in patients suffering symptomatic peripheral vascular disease. The researchers applied comprehensive screening procedures and fasting homocysteine assays to 150 patients. They noted that a quarter of patients had thrombophilia and a third had hyperhomocysteinaemia.

Concerns about dependence on prescribed analgesia may compromise pain management, but there was previously little reliable evidence about substance dependence among patients with sickle cell disease (SCD). We conducted in-depth, semi-structured interviews with SCD patients in London, UK, to assess DSM-IV symptoms of substance dependence and abuse. Criteria were applied to differentiate between pain-related symptoms, which corresponded to the DSM-IV symptoms but involved analgesics used to control pain, and non-pain-related symptoms, which involved analgesic use beyond pain management. Pain-related symptoms are informative about how the pattern of recurrent acute pain in SCD may make patients vulnerable to perceptions of drug dependence. Non-pain-related symptoms are informative about more stringently defined dependence on analgesia in SCD. Inter-rater reliability was high, with mean Kappa coefficients of 0.67-0.88. The criteria could be used to assess analgesic dependence in other painful conditions. Pain-related symptoms were more frequent, accounting for 88% of all symptoms reported. When pain-related symptoms were included in the assessment, 31% of the sample met the DSM-IV criteria for substance dependence, compared with only 2% when the assessment was restricted to non-pain-related symptoms. Qualitative analysis of participants' descriptions of analgesic use showed that active coping attempts (attempts to anticipate pain and avoid hospital admissions) and awareness of dependence were themes in descriptions of both pain-related and non-pain-related symptoms. Seeking a more normal lifestyle and impaired activities were themes associated with pain-related symptoms. Psychological disturbance was a theme associated with non-pain-related symptoms. The implications are for more responsive treatment of pain in SCD and greater awareness of how patients' pain coping may be perceived as analgesic dependence. Further research could examine ways that pain-related and non-pain-related symptoms of dependence may be associated with other pain coping strategies and with the outcomes of treatment for painful episodes in hospital. [ABSTRACT FROM AUTHOR]

We describe 21 patients with severe and life-threatening autoimmune cytopenias resistant to standard immunosuppression who were treated with the monoclonal antibody Campath-1H. Four patients had autoimmune neutropenia, four had autoimmune haemolytic anaemia, four had pure red cell aplasia, one had immune thrombocytopenia purpura (ITP), three had autoimmune haemolytic anaemia and ITP (Evan's syndrome), three had autoimmune pancytopenia (ITP, autoimmune neutropenia and autoimmune haemolytic anaemia), one had ITP (associated with acquired Glanzmann's disease) and autoimmune neutropenia, and one had ITP and red cell aplasia. Campath-1H was administered at a dose of 10 mg/d as an intravenous infusion for 10 d. Responses were seen in 15 patients, which were sustained in six. Relapse occurred in eight patients after Campath-1H treatment. Patients entering the study later, received cyclosporine after Campath-1H in an attempt to reduce the incidence of relapse. Three patients received a second course of Campath-1H; all responded but later relapsed. Fourteen patients are alive at a median of 12 months (range 4–61) after Campath-1H. Campath-1H represents an alternative therapeutic option for severe, refractory autoimmune cytopenias. [ABSTRACT FROM AUTHOR]

Abdominal pain of presumed vasocclusive origin, often termed ‘girdle syndrome’ because of the circumferential distribution of the pain, is common in sickle cell anaemia (SCA) . Evidence of progression to bowel infarction is rare. A 27-year-old man with SCA developed chest and abdominal pain unresponsive to opiate analgesia. Abdominal X-ray showed dilated bowel loops because of partial obstruction. Despite reduction of HbS to 23% by automated red cell exchange, abdominal pain worsened. A CT scan was the most informative investigation and showed free peritoneal air. He underwent emergency hemicolectomy and reversible ileostomy formation. Histology of the resected colon was consistent with acute ischaemic colitis. Early surgical intervention remains essential in SCA when abdominal pain does not respond to maximal therapy including red cell exchange: as this case illustrates, sickle girdle syndrome has the capacity to progress to irreversible ischaemic colitis and necrotic perforation of the bowel wall. [ABSTRACT FROM AUTHOR]

Background: Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations.Methods: In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies. Healthy volunteers received a single subcutaneous injection of fitusiran (at a dose of 0.03 mg per kilogram of body weight) or placebo. The participants with hemophilia received three injections of fitusiran administered either once weekly (at a dose of 0.015, 0.045, or 0.075 mg per kilogram) or once monthly (at a dose of 0.225, 0.45, 0.9, or 1.8 mg per kilogram or a fixed dose of 80 mg). The study objectives were to assess the pharmacokinetic and pharmacodynamic characteristics and safety of fitusiran.Results: No thromboembolic events were observed during the study. The most common adverse events were mild injection-site reactions. Plasma levels of fitusiran increased in a dose-dependent manner and showed no accumulation with repeated administration. The monthly regimen induced a dose-dependent mean maximum antithrombin reduction of 70 to 89% from baseline. A reduction in the antithrombin level of more than 75% from baseline resulted in median peak thrombin values at the lower end of the range observed in healthy participants.Conclusions: Once-monthly subcutaneous administration of fitusiran resulted in dose-dependent lowering of the antithrombin level and increased thrombin generation in participants with hemophilia A or B who did not have inhibitory alloantibodies. (Funded by Alnylam Pharmaceuticals; ClinicalTrials.gov number, NCT02035605 .). [ABSTRACT FROM AUTHOR]

The article discusses a study on the stability of transgene expression and long-term safety of factor IX gene therapy in patients with severe hemophilia B in 2014. Based on results, a dose-dependent increase in circulating factor IX to a 1-6% level of normal value over a 3.2-year median occurred, after an intravenous infusion of AAV8 vector in all patients. The article states that the infusion resulted in a long-term therapeutic factor IX expression linked to clinical improvement.

Thrombotic thrombocytopenic purpura (TTP) may be idiopathic or secondary. We report seven TTP cases precipitated by pancreatitis. The patients were admitted with acute pancreatitis and at that time had no clinical or laboratory features of TTP. The median time to develop TTP after pancreatitis was 3 d. The patients had moderately reduced ADAMTS13 activity (mean activity 49%; normal range 66–126%) with no evidence of anti-ADAMTS13 inhibitory autoantibodies. The median number of plasma exchanges to remission was 10 (range 7–14) and no additional treatment with immunosuppression was required to maintain remission. There have been no relapses to date. [ABSTRACT FROM AUTHOR]

Abstract: Management of fisheries directed at a particular species (the target) is often complicated by the capture of other species (the bycatch), each of which may be subject to competing management objectives. Optimal management depends upon a good understanding of how catches of the target species vary in relation to bycatch of other species of commercial and conservation concern. This paper considers the composition of trawl catches taken on a Norway lobster (Nephrops norvegicus) ground off the NE coast of England, examining the factors that determine catch rates of Nephrops and various commercial finfish species taken as bycatch. We describe the results of a trawl survey undertaken using four commercial vessels deploying standard commercial gear. Only about 19% of the variance in Nephrops catch rates could be accounted for by variations in local density, as measured independently by underwater television survey of Nephrops burrows. Variations in Nephrops catch rates were dominated by changes over time, particularly in relation to tidal state. Five commercial bycatch species were taken alongside Nephrops in significant quantities. Catch rates of haddock (Melanogrammus aeglefinus), whiting (Merlangius merlangus) and lemon sole (Microstomus kitt) varied independently of Nephrops, whereas catches of cod (Gadus morhua) and plaice (Pleuronectes platessa) were inversely related to Nephrops. We conclude that it is possible for the commercial Nephrops fishery to use spatial and temporal targeting to maximise catches of N. norvegicus whilst minimising the bycatch of some fish species. If catch statistics are used to identify Nephrops-directed fishing métiers for fishery management purposes it is vital that data are examined at the level of individual hauls or fishing trips. Aggregation of data at a higher level risks obscuring the effectiveness with which the fishery is targeted at Nephrops. [Copyright &y& Elsevier]

Epidemiology data on multiple myeloma (MM) occurrence and outcome is inconsistent whilst a major limitation of randomized controlled trials is selection bias. We present a population-based analysis of patients diagnosed with MM in the South Thames area, which comprises 5·4 million adult inhabitants. A total of 855 cases of MM were ascertained between 1999 and 2000 in a collaborative project involving haematologists and the Thames Cancer Registry. The age-standardized rate was 3·29 per 100 000 and 4·82 cases per 100 000 (World Standard and European Population respectively). The median age was 73 years. The median survival for the whole group was 24 months whist it was 42 and 18 months in those aged less than 65 years and greater than 65 years respectively (P < 0·001). This population study has shown a higher incidence than previously reported in the UK and Europe and provides a benchmark for future studies. If survival is to be improved, future clinical trials and health care planning should consider patients over 65 years of age. [ABSTRACT FROM AUTHOR]

The functional and morphological changes induced by recombinant interleukin 2 (IL-2) were studied in purified B cells from patients with untreated B chronic lymphocytic leukaemia (B-CLL). In eight of nine patients, purified B-CLL cells increased their DNA synthesis in response lo IL-2 without preactivation in vitro. This response, studied in detail in three patients, was dose dependent and reached a maximum on day 5 or 6. IL-2 induced or increased IgM secretion in cultures from five of the nine patients studied. Two of this responsive group were particularly interesting as IL-2 not only stimulated IgM secretion but also induced the secretion of IgG, Immunoglobulin production was invariably monoclonal. B CLL cells incubated with IL-2 showed distinct morphological changes including an increase in the size of cytoplasm and enlargement of nuclei together with the appearance of nucleoli. These changes were present in all IL-2 treated cultures but were more pronounced in those containing immunoglobulin secreting cells. None of the IL-2 induced changes appeared to correlate with the clinical stage of the disease or the level of Tac antigen expression on the freshly isolated CLL B cells. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the successful treatment of accelerated vascular rejection in a highly immunized renal transplant recipient with immunoadsorption and 15-deoxyspergualin.

Examines the risks of an acute myocardial infarction on patients with thrombophilia in Great Britain. Increase on the level of mortality rate; Description on the physical condition of the patients; Level of survival.