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Biomedical subjects

T B Wallington

Publications and source records attributed to T B Wallington.

At least 19 recordsLinked to original sources

Survey of clinical allergy services provided by clinical immunologists in the UK.

BACKGROUND: The UK National Health Service is failing to meet the need for diagnosis and treatment of allergic disorders, which are common and increasing in prevalence. The House of Commons select committee report on allergy services highlighted the inequalities and urgent need for investment. AIM: To survey the allergy workload provided by clinical immunologists to inform service planning and resource allocation. METHODS: The allergy services performed by clinical immunologists during a 12 month period from 1 April 2003 to 31 March 2004 were surveyed by means of a questionnaire via supra-regional audit groups. RESULTS: The immunology centres surveyed serve 32 million people and offer almost the complete repertoire of a specialised allergy service. There were large variations in clinic capacity, new referrals, appointment duration, and service configuration. Services were largely consultant delivered, but availability of joint clinics with paediatricians and anaesthetists was locally variable. Novel service delivery models utilising nurses and clinical assistants have been developed and merit further investigation. CONCLUSION: Consultant immunologists and trainees currently make a major contribution to the development and provision of specialised allergy services. Consultant immunologists will probably remain key providers of tertiary level allergy care in the UK in the long term (in line with other countries) and will be pivotal in supporting and developing the provision of equitable national access to specialist allergy services in a timely manner. Rapid progress in developing the new specialty of allergy and securing better access to services for patients in the short term will be best served by strengthening the collaborative relationship between allergists and clinical immunologists.

Adult↗

Dermatomyositis treated with high-dose intravenous immunoglobulins and associated with panniculitis.

Polymyositis and dermatomyositis are idiopathic inflammatory myopathies characterized by subacute symmetrical weakness of proximal limb and trunk muscles. Dermatomyositis is distinguished from polymyositis by the presence of rash. We describe an adult patient with treatment-resistant childhood-type dermatomyositis who made a good response to high dose intravenous immunoglobulins. Additionally, there was evidence of panniculitis which is an unusual histopathological finding in dermatomyositis.

Adult↗

A prospective controlled crossover trial of a new heat-treated intravenous immunoglobulin.

Twenty-one patients with primary immunoglobulin deficiency were enrolled in a crossover study to test the efficacy and safety of Alphaglobin in comparison with the licensed preparations Sandoglobulin and Gamimune. There was no statistical difference in these parameters between Alphaglobin and Sandoglobulin/Gamimune. The level of total serum IgG and specific IgG to pneumococcal polysaccharides was similar in individual patients when they were receiving Alphaglobin or one of the other products. Transient increases in serum alanine transferase occurred in five patients on Sandoglobulin/Gamimune and two patients on Alphaglobin. Some patients showed a rise in total serum IgM afterwards, indicating a response to infection. However, serum hepatitis C virus (HCV) RNA was not found during the alanine transferase (ALT) rises, and IgM antibody to hepatitis A virus (HAV) was negative afterwards. We conclude that Alphaglobin is a safe, well tolerated and clinically efficacious treatment for patients with primary antibody deficiency.

Adult↗

Clinical relevance of testing for antineutrophil cytoplasm antibodies (ANCA) with a standard indirect immunofluorescence ANCA test in patients with upper or lower respiratory tract symptoms.

BACKGROUND: Reports from specialist nephrological centres have suggested that the antineutrophil cytoplasm antibody (ANCA) test is highly specific and sensitive for patients with Wegener's granulomatosis. To determine the usefulness of the ANCA test in everyday respiratory practice the results of the test were audited in all patients in the south west of England with respiratory symptoms who underwent the test. METHODS: The results of all 335 patients who had presented with upper or lower respiratory tracts symptoms, or both, and were tested for ANCA by the indirect ANCA test in 1990, as recommended in the broadsheet of the British Association of Clinical Pathologists, were audited. Case notes and necropsy reports were available for review in 231 cases (69%), and in the remainder information was obtained by a standard questionnaire. RESULTS: There were 106 positive results, 45 (44%) from patients with Wegener's granulomatosis. The sensitivity and specificity of a positive ANCA test result in this study were 65% and 77% respectively. For a diagnosis of Wegener's granulomatosis the sensitivity and positive predictive accuracy of a positive cytoplasmic ANCA (c-ANCA) test were greater than of a positive perinuclear ANCA (p-ANCA) test. There were 61 positive tests in 266 patients who did not have Wegener's granulomatosis (23%); of these 27 were from patients with infection, 10 with fibrotic lung disease, nine with underlying connective tissue disease, seven with malignancy, and five following pulmonary emboli. Most of these positive ANCA results were p-ANCA (69%) rather than c-ANCA (31%). Serial ANCA requests were made in 15 cases of patients without Wegener's granulomatosis who had an initial positive ANCA test result. In all cases the ANCA tests subsequently became negative. CONCLUSIONS: In this study the sensitivity and specificity of a positive ANCA test result were less than that reported from specialised centres. However, the test was found to be useful in clinical practice, especially c-ANCA, in conjunction with clinical symptoms of respiratory pathology and evidence of renal disease.

Adolescent↗

Clinical significance of anti-neutrophil cytoplasm antibodies detected by a standardized indirect immunofluorescence assay.

We assessed the use of a standardized antineutrophil cytoplasm antibody (ANCA) test in diagnosing Wegener's granulomatosis (WG), microscopic polyarteritis (mPA) and systemic vasculitis (SV). All samples (n = 779) tested for ANCA at our laboratory were identified, and clinical information was obtained for 783/779 patients by questionnaire, and by visits where necessary. The combined prevalence of WG/mPA/SV was 123/738 (17%). The ANCA test was positive in 48/68 WG patients (71%; 38 cANCA, 10 pANCA), 22/43 mPA patients (51%; 12 cANCA, 10 pANCA) and 3/12 SV patients (25%). WG and mPA patients in remission had similar frequencies of positive ANCA to those with active disease. The sensitivity and specificity for WG (71% and 80%) and mPA (51% and 80%) were lower than previously reported. In this high-prevalence population, the overall (WG/mPA/SV) positive predictive value was only 40%, and the sensitivity 59%. Only 29% of positive tests were from patients with active disease. Overall, 78% of test results gave a 'true' prediction. On this basis, a diagnosis of necrotizing vasculitis (WG/mPA/SV) can be neither made nor refuted by ANCA test alone.

Adolescent↗

Hydralazine predisposes to acute cutaneous vasculitis following urography with iopamidol.

We report a 60-year-old woman with renovascular hypertension who developed a severe cutaneous vasculitis 24 h after the injection of iopamidol during urography. A review of the literature suggests that her concomitant hydralazine therapy probably predisposed her to this reaction, as similar reactions have occurred in systemic lupus erythematosus, and hydralazine can induce a LE-like syndrome. We recommend that urography should be avoided in patients receiving hydralazine.

Contraindications↗

Immune reconstitution after BMT in children.

Serial assessment of peripheral blood T and B cell recovery and serum immunoglobulins was performed in 19 children for the first year following BMT and compared with normal values established from healthy children. Immunophenotypic analysis on bone marrow was performed in selected cases by Southern blotting of the immunoglobulin heavy chain (IgH) gene. We found no significant differences between T cell-replete or depleted allogeneic bone marrow transplants. Lymphocyte numbers were low until 9 months post-BMT. T cell numbers (CD2, CD3, CD5) were also low until 12 months but B cell numbers (CD19) became normal at 3 months. Both CD4+ and CD8+ T cell subsets were low post-BMT with depression of CD4+ greater and more prolonged than that of CD8+. No overshoot of CD8+ was seen. The principal effect of GVHD or its treatment was further depression of CD4+ cells but with no increase in CD8+; recovery of B cells was also delayed. Recovery of IgG was slow with only six of 11 children reaching an age-adjusted normal level by 1 year, whereas there was more rapid recovery of IgM and IgA. Several children had an increase in lymphocytes of immature appearance in their bone marrow at varying times post-BMT with increased cells of phenotype CD19+, CD10+, HLA-DR+ and TdT+. In each case Southern blotting showed a germline pattern of the IgH indicating a polyclonal early B cell regenerative population.

Adolescent↗

Accessory cell damage and loss of overall white cell viability inhibit lymphocyte responses after ultraviolet-B irradiation but without evidence of in vitro suppression.

The effect of different doses of ultraviolet B irradiation (UVR) on the proliferative responses of Balb/c spleen cells has been tested. In 72-hour cultures, there was dose-dependent suppression of proliferation in response to phytohemagglutinin (PHA). Cell viability after UVR was found to be reduced in a dose- and time-dependent manner. Proliferation increased by greater than 100 percent after low-dose (20 J/m2) UVR when either normal or gamma-irradiated peritoneal cells were added to the cultures, but not at higher doses. Delaying UVR until 24 hours after stimulation of cultures with PHA did not substantially increase [3H]-thymidine uptake. Stimulation of mixtures of UV-irradiated and control cells or incorporation of medium conditioned with UV-irradiated cells provided no evidence of suppression of proliferation. The accessory cell population is an important target for UVR, but cells are physically damaged to the extent that, at higher doses, the response to PHA stimulation cannot be restored.

Animals↗

Progressive multifocal leucoencephalopathy, sclerosing cholangitis, bronchiectasis and disseminated warts in a patient with primary combined immune deficiency.

A 24 year old man presented with an unusual primary combined immune deficiency syndrome characterised by a profound lymphopenia of CD4 cells, selective serum IgG2 subclass deficiency, poor polysaccharide antibody responses, disseminated warts, recurrent sinopulmonary infection and bronchiectasis. The developed progressive multifocal leucoencephalopathy (PML) in association with sclerosing cholangitis. Progressive multifocal leucoencephalopathy (PML) usually occurs as an opportunistic infection in patients with secondary defects in cellular immunity.

Adult↗

Laboratory investigation in the diagnosis of pulmonary thromboembolism.

Laboratory findings were compared with lung scans in a prospective study of 260 patients undergoing ventilation-perfusion (V/Q) lung scanning for suspected pulmonary thromboembolism. The best discrimination between different lung scan results was obtained from the level of plasma cross-linked fibrin degradation products, every patient with a scan indicating a high probability of thromboembolism having detectable levels. An acute phase response was demonstrated in patients with pulmonary thromboembolism by a raised neutrophil count and elevated levels of plasma fibrinogen and serum C-reactive protein. A normal level of serum C-reactive protein and/or plasma cross-linked fibrin degradation productions in blood taken within 4 days of onset of symptoms virtually excluded the diagnosis of pulmonary thromboembolism. Detection of free plasma DNA was not helpful in discriminating between groups with different lung scan results. Discriminant analysis was used to assess the variables examined and to derive diagnostic models. An accuracy of 78 per cent was obtained with one model for classifying test patients according to the three lung scan classes of low, intermediate and high probability. A second model, for distinguishing patients with a low and a high probability of pulmonary thromboembolism on the basis of lung scans, and a third for predicting those with a low probability on lung scan, were accurate in 94.6 per cent and 83.5 per cent of patients respectively. Discriminant models could be used in the diagnosis of pulmonary thromboembolism, especially when diagnostic imaging is not available.

C-Reactive Protein↗

Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light.

Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m2 and abolished at 50 J/m2. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m2 of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m2) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m2. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m2 survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m2 survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m2) and 2 of 9 (100 J/m2). These data indicate that UV-B irradiation inhibits lymphocyte reactivity and can prevent GVHD. However, there is clear in vitro and in vivo evidence of stem cell damage, such that autologous marrow recovery was demonstrated in a proportion of recipients. In parent----F1 UV-irradiated transplants, sustained hematopoietic recovery was effected in the majority by donor stem cells.

Animals↗

Immunomodulation by ultraviolet light: clinical studies and biological effects.

The interest of immunologists in ultraviolet (UV) irradiation stems from observations made in vitro and in vivo. In vitro, UV irradiation inhibits mitogen and mixed lymphocyte culture (MLC) responses and in vivo, it can induce cutaneous anergy, apparently via suppressor cells and serum factors. At present much interest is focused on the possible use of UV irradiation to permit transfusion without allosensitization and transplantation without either rejection or graft-versus-host disease (GVHD). Here, Derwood Pamphilon and colleagues discuss the current uses and potential of UV irradiation in transfusion and transplantation and relate these to experimental evidence on its effects at the cellular level.

Animals↗

Plasma exchange in the treatment of Guillain-Barré syndrome: experience in a sub-regional referral centre.

Plasma exchange became popular in the treatment of Guillain-Barré syndrome with the publication in 1985 of results by the Guillain-Barré Study Group. Since then we have treated 24 patients referred for plasma exchange. We have audited their outcome and compared this with the results of patients in the treatment arm of the USA Study. Our patients were of comparable age and clinical severity and had similar duration of illness before starting plasma exchange. Nine of our patients required ventilation for a median of 24 days. The median time to improve one clinical grade was 19 days which compared well with the Study Group results. We have shown that plasma exchange may be safely performed in a district general hospital in a setting appropriate to the patient's clinical condition. We concur with the central conclusion of the Study, that if treatment is started early in the disease, the patient's outcome is improved.

Adult↗

Transient erythroblastopenia of childhood with CD10, TdT, and cytoplasmic mu lymphocyte positivity in bone marrow.

Over three years, three children presented with anaemia, reticulocytopenia, and marrow erythroblastopenia. A pronounced lymphocytosis was also evident in two of the marrow aspirates, with increased numbers of cells bearing the immunophenotype TdT+, CD10+ HLA DR+, and cytoplasmic mu +, and reported to be compatible with acute lymphoblastic leukaemia (ALL). The clinical course of the illness was fully compatible with transient erythroblastopenia of childhood (TEC), and all three children remained well one to four years after initial presentation. It is concluded that increased numbers of lymphoid cells with a common or pre-B ALL phenotype may be found in bone marrow aspirates of children with TEC, and should not be misdiagnosed as acute leukaemia.

Anemia↗