Effect of virucidal heat treatment on proteins in human factor VIII concentrates

Intermediate-purity and fibrinogen-poor factor VIII concentrates were heated in the lyophilized state at 60 degrees C for up to 72 hours to inactivate blood-borne viruses. The effect of heat treatment on factor VIII, von Willebrand factor (vWf), and other proteins present in the concentrates (albumin, fibrinogen, fibronectin, IgG, and IgM) was evaluated. Heat-induced protein aggregation, particularly of fibrinogen and fibronectin, occurred within 48 hours in the intermediate-purity concentrates and correlated well with decreased solubility of these products. Heated fibrinogen-poor concentrates were readily soluble and did not show protein aggregation even after 72 hours at 60 degrees C. Neither concentrate developed detectable neoantigens when tested against antisera to whole human plasma and to heated and unheated concentrates. Aggregation of the vWf molecule, detected by altered mobility in crossed immunoelectrophoresis and multimeric analysis in SDS agarose gels, occurred in heated intermediate-purity concentrates but not in fibrinogen-poor concentrates. Thus, higher-purity factor VIII concentrates withstand heat treatment better than concentrates that contain greater levels of contaminating proteins, particularly fibrinogen.     

A national survey of practice nurse involvement in mental health interventions

BACKGROUND: The move in the United Kingdom (UK) from institutional to community care has led to an inevitable increase in the involvement of practice nurses (PNs) in mental health care. Around 20 000 PNs are currently working in the United Kingdom (UK). However, the extent and nature of PN involvement in delivering mental health interventions has not been adequately explored. AIM: This study aimed to quantify practice nurses' involvement in delivering mental health interventions in primary care settings. METHOD: A questionnaire was sent to a random sample of 1500 practice nurses registered with the Practice Nurse Forum at the Royal College of Nursing. Sixty per cent of questionnaires were returned; however, once non-eligible respondents were removed an adjusted response rate of 54% was achieved. RESULTS: Practice nurses play a significant role in the assessment and treatment of mental health problems, most frequently via the administration of depot antipsychotics and the screening for depression. However, antipsychotic side-effects were infrequently monitored and PNs' understanding of treatment issues in depression is poor. These findings may be associated with the reported lack of mental health training that PNs have received. CONCLUSIONS: The findings of this study have important implications for the training of practice nurses in mental health, specifically in the areas of medication management and the detection of mental disorders.     

HIV testing preferences among pregnant women attending antenatal care and their male partners: a discrete choice experiment in Uganda

HIV testing rates remain stubbornly low among men – a crucial target population for reaching the ambitious global and regional goals of the HIV programme. In an era of declining donor funding, identifying cost-effective strategies to increase testing rates amongst men remains paramount. Antenatal care is an effective entry-point for the delivery of HIV testing services for women, and partner testing presents an important opportunity to reach their male partners. We present the results of a discrete choice experiment in Uganda, examining preferences among 824 pregnant women and 896 male partners regarding service delivery characteristics of HIV testing. Both men and women preferred nurse administered testing to self-testing (OR = 0.835; p < 0.001), oral testing over a finger-prick test (OR = 1.176; p < 0.001) and testing with a partner over testing alone (OR = 1.230; p < 0.001). Men had a preference for testing at home compared to testing at a clinic (OR = 1.099; p = 0.024), but women were indifferent regarding the testing location. The cost of testing had the biggest effect on preferences. Free testing was preferred over a cost of US$2.90 (OR = 0.781; p < 0.001) or US$2.00 (OR = 0.670; p < 0.001). Offering an incentive of US$3.40 increased men’s preferences compared to a free test (OR = 1.168; p < 0.001), although this did not affect women’s preferences. Partner testing linked to antenatal care is a potential strategy to increase testing coverage among men, particularly given the preference for partner testing – provided costs to clients remain low. Future cost-effectiveness evaluations should investigate the economic impact of reaching men using these strategies.     

A bioartificial transgenic porcine whole liver expressing human proteins alleviates acute liver failure in pigs

Background: Preventing heterologous protein influx in patients is important when using xenogeneic bioartificial livers(BALs) to treat liver failure. The development of transgenic porcine livers synthesizing human proteins is a promising approach in this regard. Here, we evaluated the safety and efficacy of a transgenic porcine liver synthesizing human albumin(h ALB) and coagulation factor VII(h FVII) within a bioartificial system. Methods: Tibetan miniature pigs were randomly subjected to differ...     

Cytokine-mediated regulation of transferrin synthesis in mouse macrophages and human T lymphocytes

Transferrin (Tf) plays an important role during immunologic activation by donating iron to activated lymphocytes. Therefore, synthesis by lymphomyeloid cells has been investigated. Mouse macrophages and macrophage cell lines synthesized Tf, with levels being markedly increased by gamma-interferon (gamma-IFN) and, to a lesser extent, by interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor alpha (TNF alpha). Tf was also produced by phytohemagglutinin-stimulated human T cells and two T-cell lines and was increased by IL-2. Even after appropriate activation, none was synthesized by human macrophages or monocytic cell lines or by mouse T cells, T-cell lines, or thymus cells. In both species, B-lineage cell lines were negative. Tf was also synthesised by macrophages from congenitally hypotransferrinemic mice and was responsive to gamma-IFN, but levels were lower than those from normal controls. Synthesis by human and murine hepatoma cells was increased by IL-6 but unaffected by IL-1, TNF alpha, or gamma-IFN. Iron decreased synthesis by hepatoma cells but had no effect on the lymphomyeloid cells. Tf mRNA levels paralleled protein synthesis, suggesting that regulation was pre-translational. Thus, Tf synthesis by lymphomyeloid cells is regulated differently from hepatic synthesis, which is consistent with the suggestion that Tf may act in a paracrine (mouse) or autocrine (human) manner on activated lymphocytes.     

Waldenstrom's macroglobulinemia with an IgM paraprotein that is both a cold agglutinin and a cryoglobulin and has a suppressive effect on progenitor cell growth

BACKGROUND: A patient with Waldenstrom's macroglobulinemia was admitted to the hospital with fever, leg pain, and dyspnea. The patient had gas gangrene of the left leg that required above-the-knee amputation. Plasmapheresis was instituted to treat hyperviscosity. STUDY DESIGN AND METHODS: The patient's serum contained an IgM-kappa paraprotein, a cryoglobulin, and a cold agglutinin. The serum was studied. RESULTS: The patient's red cells typed as A1, Rh-positive. The direct antiglobulin test was negative. The serum contained a cold agglutinin with anti-Pr cold agglutinin specificity (titer 4096). Maximal thermal range was 30 degrees C. Following dithiothreitol treatment, the cold agglutinin activity disappeared. The serum IgM concentration in the tested sample was 62.3 g per L. The cold agglutinin titer in the supernatant after removal of the cryoglobulin was 256, and the IgM level was 0.31 g per L. Redissolving the cryoglobulin in a equivalent volume of saline resulted in a cold agglutinin titer of 4096 and an IgM level of 68.4 g per L. These results indicate that the cryoglobulin and the cold agglutinin are the same paraprotein. Serum protein electrophoresis using agarose gel and immunofixation of the serum revealed an IgM-kappa monoclonal band. Progenitor cell assays were performed by adding the patient's serum at final concentrations of 0, 1, 5 and 10 percent (vol/vol) to patient's and normal donor's peripheral blood mononuclear cells. Inhibition of burst-forming units- erythroid and colony-forming units-granulocyte/macrophage by the patient's serum was demonstrated. Appropriate controls and the use of the serum of another patient with Waldenstrom's macroglobulinemia did not suppress progenitor cell growth. The patient's serum inhibited colony formation in a dose-response fashion. CONCLUSION: Reports of cryoprecipitable cold agglutinins are rare. This case is unusual because the IgM-kappa paraprotein was also a cold agglutinin with anti- Pr specificity and erythroid and granulocyte-macrophage progenitor cell- suppressive properties.