5 research outputs found
Phase tracking of sub-10 fW heterodyne optical signals for precision laser displacement metrology in space
No full textA preliminary investigation into the risk factors associated with cellulitis of the lower limb
No full textCellulitis is an infective/inflammatory skin condition costing 426,000 bed days per year. The legs are most frequently affected and 18-20% of patients suffer from recurrent attacks. Bacteria are thought to be causal but are rarely identified, therefore antibiotic treatment is empirical and currently the only means of prophylaxis. Previous studies have cited athlete’s foot, skin vulnerability and oedema as risk factors for cellulitis and there may also be a relationship with the immune response. This preliminary study was designed to evaluate these risk factors and identify areas for further investigation.Patients were matched with controls (N = 12 + 12 controls) by age, sex and mobility. Participants attended twice (during treatment and again 6 weeks after clinical resolution). Foot scrapings were cultured to examine the flora and blood samples taken to determine white cell types and numbers, cytokine levels and markers specific to fungal infection. Physiological measurement techniques were used to assess skin function. Psychological stress levels were evaluated and medical history recorded.Fewer dermatophytes were grown from the feet of patients as compared to matched controls. Amongst patients blood profiling showed evidence of increased neutrophil count post episode and levels of IL-12 and IL-8 also reached near significance in this group. Physiological tests for skin blood flow, water loss and pH produced results consistent with cellulitic skin but persisting oedema was significantly higher in the patient group and characterised by loss of structure in the dermal tissues. Ipsilateral injuries, allergies, history of other bacterial infections, excessive life time prescription of antibiotics and levels of psychological stress, evaluated by a questionnaire, were also found to be significantly higher in the patient group. No evidence was produced to show any differences between acute and recurrent populations.This preliminary study into the potential risk factors for cellulitis indicates that some factors merit further investigation. Larger studies are required to substantiate results
RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients
No full text\ua9 2022, The Author(s). Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA
Clinical and functional studies of autoimmune disorders of neuromuscular transmission
No full textInherited and acquired disorders of the neuromuscular junction are an important cause of muscle weakness and fatigability. In this thesis I focus on the autoimmune disorders of neuromuscular transmission. Myasthenia Gravis (MG) is the most common of these diseases and is typically caused by antibodies against the post-synaptic acetylcholine receptor. Lambert Eaton Myasthenic Syndrome (LEMS) is a pre-synaptic disorder typically caused by antibodies against voltage gated calcium channels (VGCC). With regard to LEMS, my main aim was to gain a more complete understanding of the pathomechanisms of the disease. To date, the direct effect of LEMS IgG on presynaptic neurotransmitter release had not been investigated in detail. I examined how LEMS IgG affects neurotransmitter release by imaging action potential dependent vesicle exocytosis using a fluorescent dye. I found that LEMS IgG significantly inhibited the rate of synaptic vesicle release but this effect was lost in synapses from a Cacna1a knockout mouse. These data provide direct evidence that LEMS is caused by impaired neurotransmitter release due to an effect on P/Q-type VGCCs. With regard to MG, I studied the long-term outcome of patients with thymomatous and non-thymomatous MG after thymectomy and found that in general the outcome was favourable in the majority of patients with 34% of patients achieving complete stable remission. I also reviewed the long-term outcome of patients after a severe exacerbation of MG requiring ITU admission. Despite the significant mortality associated with severe exacerbations of MG, it was found that specialised neuro-intensive care was associated with a good long-term prognosis in the majority of patients. There were no significant differences in outcome in those with early or late onset MG. Overall the data presented in this thesis provide new insights into the pathomechanisms of LEMS IgG and provide new information regarding the long-term outcome of patients with MG
