Practical management of food allergy

Food allergy is on the increase, particularly in Africa and Asia. Significant regional variations in the key food allergens are determined by diet and inhalant allergy cross-reactivities. A good clinical history, supported by appropriate validated in vivo and in vitro tests, is the bedrock of diagnosis. Clinicians should be aware of potential hidden allergens in food substitutions. Accurate food labelling for key allergens by manufacturers is required but may not be readily available.http://www.journals.co.za/content/journal/cacipm2021Paediatrics and Child Healt

An unusual cause of granulomatous disease

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disorder of phagocytic cells caused by an inability to generate active microbicidal oxygen species required kill certain types of fungi and bacteria. This leads to recurrent life-threatening bacterial and fungal infections with tissue granuloma formation. CASE PRESENTATION: We describe a case of X-linked Chronic granulomatous disease (CGD) diagnosed in an 18-year-old male. He initially presented with granulomatous disease mimicking sarcoidosis and was treated with corticosteroids. He subsequently developed Burkholderia cepacia complex pneumonia and further investigation confirmed a diagnosis of CGD. CONCLUSION: Milder phenotypes of CGD are now being recognised. CGD should be considered in patients of any age with granulomatous diseases, especially if there is a history of recurrent or atypical infection

A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL

Lipidome profile of fluids and tissues is a growing field as the role of lipids as signaling molecules is increasingly understood, relying on an effective and representative extraction of the lipids present. A number of solvent systems suitable for lipid extraction are commonly in use, though no comprehensive investigation of their effectiveness across multiple lipid classes has been carried out. To address this, human LDL from normolipidemic volunteers was used to evaluate five different solvent extraction protocols [Folch, Bligh and Dyer, acidified Bligh and Dyer, methanol (MeOH)-tert-butyl methyl ether (TBME), and hexane-isopropanol] and the extracted lipids were analyzed by LC-MS in a high-resolution instrument equipped with polarity switching. Overall, more than 350 different lipid species from 19 lipid subclasses were identified. Solvent composition had a small effect on the extraction of predominant lipid classes (triacylglycerides, cholesterol esters, and phosphatidylcholines). In contrast, extraction of less abundant lipids (phosphatidylinositols, lyso-lipids, ceramides, and cholesterol sulfates) was greatly influenced by the solvent system used. Overall, the Folch method was most effective for the extraction of a broad range of lipid classes in LDL, although the hexane-isopropanol method was best for apolar lipids and the MeOH-TBME method was suitable for lactosyl ceramides

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Studies on the functional heterogeneity of rat T cells using monoclonal antibodies

A new monoclonal antibody against rat lymphocytes is described. This antibody, designated MRC-OX22, recognises an antigen found on all peripheral B cells, all suppressor/cytotoxic lymphocytes, but only on some helper cells, as defined by the W3/25 antibody. The antigen is found on a significant number of bone marrow cells, but only on 3% of thymocytes, which were located by immunoperoxidase staining at the cortico-medullary junction. The phenotypic division of the W3/25+ peripheral T cells, is mirrored functionally. By using the popliteal lymph node assay, and the induction of lethal graft-versus-host disease as indicators of alloreactivity, it is found that the alloreactive T cells have the phenotype MRC-OX22+ ,W3/25+. In contrast, using an adoptive transfer system to assess T cell help for B cell antibody production, the phenotype of the Thelper for B cells is shown to have the phenotype MRC-OX22-, W3/25+. Evidence is also presented that the phenotype of the Thelper cell for B cells is stable after priming and boosting. The phenotype of the memory B cell is shown to be MRC-OX22+, and the cell responsible for allogeneic suppression is also shown to be MRC-OX22+, using the adoptive transfer system for antibody formation. The significance of the functional heterogeneity of the W3/25+ subset is discussed, and the biochemical nature of the antigen recognised by MRC-OX22 is reviewed, and compared with possible homologues in mouse and man.</p

Tele-rehabilitation: video-conferencing for delivery of interventions for people with Chronic Fatigue Syndrome

Background: The delivery of services to those who are house bound or those that are unable to access transport, especially within a rural locality were identified as issues by the North Cumbria Chronic Fatigue Syndrome (CFS/ME) team. Technology that would enable the team to work with clients in their own home; without the resource implications of providing a domiciliary-based service was explored. The rationale was to provide a service to clients that have difficulty accessing clinics, particularly the severely affected and to create a more inclusive ‘closer to home’ service provision. The investigation was divided into four phases:\ud • Systematic review of the literature\ud • Scoping exercise via a questionnaire to all current clients\ud • Feasibility and acceptability pilot with 5 clients\ud • Development of larger cohort observational study\ud \ud Results: Phases 1–3 are complete. The review identified that in-home desktop video-conferencing is likely to be well received by patients and to be equivalent to in-person therapy in terms of clinical outcomes. Cost effectiveness of systems was shown to be reliant on initial outlay and amount of usage, and that such services could result in significant savings in time and money for patients [1]. The scoping exercise identified that there was a need for tele-rehabilitation to address the difficulties this population face in travelling to appointments, and that it was feasible as most people already had access to computers with broadband internet connection. The pilot study showed that PC-based video-conferencing in a real-life situation, linking people’s homes to a clinical base, is technically feasible and resulted in positive feedback from clients and the therapist. Technology functioned effectively, facilitating satisfactory interactions between clients and therapist. Technical problems were judged by clients and therapist not to interfere with the interaction. An implementation guide including tips for best practice and troubleshooting has been produced. This project to date has had an impact on the service and the patients. The interventions delivered by video-conferencing have resulted in high satisfaction levels for patients and have produced similar clinical outcomes to in-person delivery. This mode of delivery is being used for both consultant review sessions and patient to therapist interactions. The use of video-conferencing is now embedded into the service and offered to patients when travel or level of disability could affect attendance due to difficulties with transport or level of symptoms.\ud \ud Conclusions: It is feasible to use video-conferencing as a means of delivering interventions for people with chronic fatigue in rural communities. Further investigation is required to understand the differences between clinic-based and video-conferencing interventions over time

Behavioural Interventions to Reduce Nickel Exposure in a Nickel Processing Plant.

Nickel is a widely used material in many industries. Although, there is enough evidence that occupational exposure to nickel may cause respiratory illnesses, allergies and even cancer, it is not possible to stop the use of nickel in occupational settings. Nickel exposure, however, can be controlled and reduced significantly in workplaces. The main objective of this study was to assess if educational intervention of hygiene behaviour could reduce nickel exposure among Indonesian nickel smelter workers. Participants were randomly assigned to three intervention groups (n = 99). Group one (n = 35) received only an educational booklet about nickel, related potential health effects and preventive measures, group two (n = 35) attended a presentation in addition to the booklet, and group three (n = 29) received personal feedback on their biomarker results in addition to the booklet and presentations. Pre and post intervention air sampling was conducted to measure concentrations of dust and nickel in air along with worker's blood and urine nickel concentrations. The study did not measure significant differences in particles and nickel concentrations in the air between pre and post interventions. However, we achieved significant reductions in the post intervention urine and blood nickel concentrations which can be attributed to changes in personal hygiene behaviour. The median urinary nickel concentration in the pre-intervention period for group one was 52.3 µg/l, for group two 57.4 µg/l and group three 43.2 µg/l which were significantly higher (p&lt; = 0.010) than those measured in the post-intervention period for each of the groups with 8.5 µg/l, 9.6 µg/l and 8.2 µg/l, respectively. A similar pattern was recorded for serum nickel with significantly (p &lt;0.05) higher median concentrations measured in the pre-intervention period for group one 1.7 µg/l, and 2.0 µg/l for group 2 and group 3 compared with the post intervention median serum nickel levels of 0.1 µg/l for all groups. The study showed that educational interventions can significantly reduce personal exposure levels to nickel among Indonesian nickel smelter workers

Falsely normal C4 in a case of acquired C1 esterase inhibitor deficiency

A 59‐year‐old lady presented with recurrent angioedema without urticaria. The clinical history and examination were consistent with an acquired C1 esterase deficiency secondary to lymphoproliferative disease. Despite a low C1 esterase level, the C4 level assayed by nephelometry on our automated analyser was normal. Analysis using different nephelometric analysers revealed consistently low C4, despite consistent normal readings in our analyser. Further investigation revealed an IgM‐κ paraprotein that seemed to interfere with both this and haematology coagulation assays. Splenic marginal zone lymphoma was confirmed on bone marrow biopsy. Monoclonal paraproteins may interfere with nephelometric, turbidimetric and immunological assays in a non‐antibody‐specific manner and should be considered when there are unusual or unexpected results, particularly in a patient with lymphoproliferative disease