New uses for IVIgG immunoglobulin therapies.
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Biomedical subjects
Publications and source records attributed to T Wallington.
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BACKGROUND AND OBJECTIVES: The results of quality monitoring leucocyte counts were analysed nationally for the first 2 years of universal leucocyte depletion (LD), spanning the time-period before and after standardization of the counting and LD methods. The objectives were twofold: first to determine whether the implementation strategy was effective in achieving the LD specification (< 5 x 10(6) leucocytes in 99% of components with 95% statistical confidence); and second, whether quality monitoring was able to detect potential non-conformance. MATERIALS AND METHODS: Residual leucocytes were counted using Beckman Coulter or Becton Dickinson (BD) flow cytometers and reagents. Data were collected into standardized analysis software (NWA Quality Analyst) for local trend analysis and checks for conformance to process specification, and collated centrally. Analysis was performed for six time-periods between January 1999 and March 2001. Specification failures were analysed to determine the likelihood of extreme failure. Statistical process monitoring was adjusted to suit LD processes. RESULTS: Data from red cells in optimal additive solution (OAS), filtered either as whole blood or red cell concentrates, and platelet pools improved significantly over the 2-year period with specification failures falling from 0.35%, 0.48% and 0.56%, respectively, in January-June 1999 to 0.06%, 0.01% and 0.04% in January-March 2001. Specification failures in red cells in OAS LD for the period January-December 2000 showed only 0.02% with a leucocyte count of > 30 x 10(6)/unit. Extreme failures are now very rare. Monitoring methods have been effective in detecting process change and drift. CONCLUSION: LD performance varies between different LD systems, but monitoring has proved sufficiently robust to detect processes that perform poorly. The chosen specification has been both achievable and appropriate to the systems in use. Standardization of the counting method is central to the ability to monitor and analyse results effectively across the whole service.
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Reductions in stratospheric ozone (O3) cause increased penetration of ultraviolet-B (UV-B) radiation to the troposphere, and therefore increases in the chemical activity in the lower atmosphere (the troposphere). Tropospheric ozone levels are sensitive to local concentrations of nitrogen oxides (NOx) and hydrocarbons. Model studies suggest that additional UV-B radiation reduces tropospheric ozone in clean environments (low NOx), and increases tropospheric ozone in polluted areas (high NOx). Assuming other factors remain constant, additional UV-B will increase the rate at which primary pollutants are removed from the troposphere. Increased UV-B is expected to increase the concentration of hydroxyl radicals (OH) and result in faster removal of pollutants such as carbon monoxide (CO), methane (CH4), non-methane hydrocarbons (NMHCs), sulfur and nitrogen oxides, hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs). Concentrations of peroxy radicals (both inorganic and organic) are expected to increase, leading to higher atmospheric levels of hydrogen peroxide (H2O2) and organic peroxides. The effects of UV-B increases on tropospheric O3, OH, methane, CO, and possibly other tropospheric constituents, while not negligible, will be difficult to detect because the concentrations of these species are also influenced by many other variable factors (e.g., emissions). Trifluoroacetic acid (TFA, CF3COOH) is produced in the atmosphere by the degradation of HCFC-123 (CF3CHCl2), HCFC-124 (CF3CHFCl), and HFC-134a (CF3CH2F), which are used as substitutes for ozone-depleting substances. The atmospheric oxidation mechanisms of these replacement compounds are well established. Reported measurements of TFA in rain, rivers, lakes, and oceans show it to be a ubiquitous component of the hydrosphere, present at levels much higher than can be explained by reported sources. The levels of TFA produced by the atmospheric degradation of HFCs and HCFCs emitted up to the year 2020 are estimated to be orders of magnitude below those of concern, and to make only a minor contribution to the current environmental burden of TFA. No significant effects on humans or the environment have been identified from TFA produced by atmospheric degradation of HCFCs and HFCs. Numerous standard short-term studies have shown that TFA has, at most, moderate toxicity.
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Previous reports have suggested a relationship between changes in indirect immunofluorescence antineutrophil cytoplasm autoantibody (ANCA) titres and disease activity in patients with Wegener's granulomatosis (WG). We analyzed retrospectively the data from 37 patients with biopsy-proven WG during a median follow-up period of 34 (range 8-60) months, during which 532 serial ANCA measurements had been made. A fourfold increase in ANCA titre and/or a positive titre following a series of negative results occurred on 82 occasions, only 19 (23%) associated with clinical relapse, 25 (31%) with intercurrent infection, and 32 (38%) when patients were considered clinically well. The sensitivity of a significant increase in ANCA titre associated with clinical relapse was 43%, with a positive predictive accuracy of 23%. The combination of an increased C-reactive protein-plasma viscosity and a significant increase in ANCA titre occurred on 37 occasions, 15 (40%) with relapse and 17 (46%) with infection. The results of this study suggest that patients with WG who have significant increases in ANCA titres should be carefully monitored. Increased immunosuppression based solely on increased ANCA titres is not justified, as if this had been practiced in this study, then a large number of patients who had infective episodes would have received additional immunosuppression from which they may not have benefited.
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Three cases of severe and irreversible alopecia occurring in patients with common variable immunodeficiency are described. In all three cases, hair loss developed after the diagnosis of immune deficiency; one of the patients also had extensive vitiligo. A fourth patient had vitiligo in the absence of alopecia. No change in the alopecia or vitiligo was noted in any patient as a result of immunoglobulin replacement therapy.
A patient with nephritic factor in the serum following an attack of disseminated herpes is described. In the majority of cases, the factor is associated with mesangio-capillary glomerulonephritis, with or without partial lipodystrophy. It has, however, been described in cases of partial lipodystrophy alone, in one patient with recurrent pyogenic infections, and in one healthy individual. It has not previously been described in an individual with disseminated viral infection.
Fc and 'complement'-mediated phagocytosis of pre-opsonized yeast has been studied in monocytes from 18 patients with SLE. Monocytes from nine of 18 patients had depressed complement-mediated phagocytosis (P = 0.0001, Fishers exact test) but only three of 18 had depressed Fc-mediated phagocytosis (NS, Fishers exact test). Although reduced complement-mediated phagocytosis was correlated with increased frequency of disease manifestations (P less than 0.003, rank correlation) there was no correlation with serum DNA or C1q binding activity, C3 or C4 levels. Serum from SLE patients with depressed phagocytosis did not inhibit phagocytosis by normal monocytes. The data suggests the presence of intrinsic abnormalities of monocyte receptor function in SLE and the nature of the 'complement' receptors involved is discussed.
We have previously described a selective defect of monocyte C3b receptor-mediated phagocytosis in patients with rheumatoid cutaneous vasculitis. We have studied a further 15 rheumatoid arthritis patients with other associated diseases and complications and have identified 4 further patients with a similar defect. Serological and cytochemical studies suggest that the defect in phagocytosis is due to the appearance of increased numbers of large nonspecific esterase-negative mononuclear phagocytes with defective C3b receptor phagocytic function rather than to receptor blockade by immune complexes.
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Fifty-three patients with early arthritis were studied longitudinally for up to 3 years. During this time, 24 developed sufficient features for definite rheumatoid arthritis (RA) to be diagnosed. The other (arthralgia patients) differed from the RA patients as, in the majority, C-reactive protein and ESR were normal and anti-nuclear antibodies or rheumatoid factors were rarely found. Moreover, in time their signs and symptoms improved or disappeared. Circulating immune complexes were detected in both groups of patients by the platelet aggregation test whereas complexes detected by abnormal Clq-binding activity were found mainly in the RA patients. Platelet-aggregating complexes were usually present in the first samples studied and disappeared in the arthralgia patients with recovery from their symptoms. In the RA patients, Clq-binding complexes appeared simultaneously or later than platelet-aggregating complexes but both tests were positive several months before RA could be diagnosed. These results suggest that immune complexes are one of the first immunological abnormalities to appear in patients with arthritis. Although the constituent antigen and antibody of complexes detected by either test are unknown, their possible nature is discussed.
IgG and IgM rheumatoid factors (IgG-RF and IgM-RF), complement and three assays for immune complexes were measured in 22 patients with rheumatoid arthritis (RA) complicated by either chronic active synovitis or vasculitis. Patients with vasculitis had relatively inactive arthritis but had higher titres of rheumatoid factors, especially IgG-RF, anticomplementary activity (ACA) and lower levels of C4 than those with synovitis. Clq-binding and platelet aggregation (PA) levels were similar in both groups. Serial measurements during cytotoxic therapy showed a close temporal relationship between the clinical features of vasculitis and levels of IgG-RF, ACA and C4 both with remission and with relapse. We suggest that immune complexes containing IgG-RF which activate complement and are detected by ACA are useful markers of rheumatoid vasculitis and may be important in its pathogenesis.