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Biomedical subjects

Susan Burge

Publications and source records attributed to Susan Burge.

6 recordsLinked to original sources

Methotrexate: improving safety profile.

Over the past 10 years, there have been 137 patient safety incidents in England associated with methotrexate prescribing. Recent reports show that Australia has similar concerns. Using the valuable tool of an audit, we reviewed our departmental prescribing practices for 49 patients with psoriasis on methotrexate. Results highlighted poor documentation that patients were receiving appropriate information sheets detailing complications of the drug. Inconsistencies between prescribers were also noted, particularly in regards to haematological monitoring. A review of the current published work and the guidelines of other leading centres was performed and consistent, evidence-based guidelines were produced for the department. Such guidelines are essential in order to minimize the recognized complications of methotrexate. Recent studies highlight procollagen peptide III as a valuable adjunct for monitoring hepatotoxicity, while there is no longer a significant role for routine recording of cumulative dose. It would be valuable to repeat the audit to ensure a change in practice and an improved adherence to common guidelines.

Blood Chemical Analysis↗

What should undergraduate medical students know about psoriasis? Involving patients in curriculum development: modified Delphi technique.

OBJECTIVE: To identify the content of a psoriasis curriculum for medical students. DESIGN: Literature review and modified Delphi technique. SETTING: Primary and secondary care in Oxfordshire and Buckinghamshire. SUBJECTS: 19 dermatologists (7 teaching hospital consultants; 6 consultants in district general hospitals; 6 registrars); 2 general practitioner senior house officers working in dermatology, 5 dermatology nurses, 7 rheumatologists, 25 general practitioner tutors, and 25 patients with chronic psoriasis. MAIN OUTCOME MEASURES: Percentage of agreement by participants to items derived from literature and our existing psoriasis syllabus. RESULTS: 71 (84.5%) of 84 questionnaires were returned. A 75% level of consensus was reached on key items that focused on the common presentations of psoriasis, impact, management, and communication skills. Students should be aware of the psychosocial impact of psoriasis, examine the skin while showing sensitivity, and be able to explain psoriasis to patients in a way that enables patients to explain the condition to others. CONCLUSIONS: The panels identified the important items for a psoriasis curriculum. The views of patients were particularly helpful, and we encourage educators to involve patients with chronic diseases in developing curriculums in the future. The method and results could be generalised to curriculum development in chronic disease.

Attitude to Health↗

Atrophic dermatofibrosarcoma protuberans.

A 48-year-old woman presented with a 20-year history of an asymptomatic depressed atrophic plaque on the abdomen. Five years earlier a punch biopsy of the same lesion had been carried out and a diagnosis of dermatofibroma was made. She was reassured and discharged. Further consultation was sought due to extension and thickening of the lesion. Re-examination of the initial and new incisional biopsy specimens, along with histochemical staining for CD34, established the diagnosis of atrophic dermatofibrosarcoma protuberans. A wide local excision was carried out. There has been no recurrence at 9 months of follow up.

Abdomen↗

Impaired trafficking of the desmoplakins in cultured Darier's disease keratinocytes.

Darier's disease is an autosomal dominantly inherited skin disorder characterized by loss of adhesion between epidermal cells, breakdown of desmosome-keratin filaments, and abnormal keratinization. ATP2A2 has been identified as the causative gene of Darier's disease. This gene encodes the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) isoform 2 pump, which transports Ca2+ from the cytosol into the endoplasmic reticulum lumen to maintain a low cytosolic Ca2+ concentration. Using indirect immunofluorescence and biochemical analysis, we investigated the distribution of key desmosomal proteins in normal human and Darier's disease keratinocytes under various calcium conditions. We show that inhibition of SERCA by thapsigargin in normal human keratinocytes impairs the trafficking of the desmoplakins, desmoglein, and desmocollin to the cell surface; these proteins show a diffuse cytoplasmic distribution and, together with plakoglobin, form detergent-insoluble aggregates. In Darier's disease keratinocytes, only the trafficking of desmoplakin is significantly inhibited; in these cells, desmoplakin forms insoluble aggregates when extracted with mild detergent. In contrast, the transmembrane proteins desmoglein and desmocollin are efficiently transported to the cell surface. These proteins, along with plakoglobin, remain equally distributed between detergent-soluble and -insoluble fractions. We also demonstrate an interaction between SERCA2 and desmoplakin during differentiation. Our results provide further insights into the critical role of calcium ATPases in maintaining epidermal integrity.

Calcium↗

Hailey-Hailey disease: molecular and clinical characterization of novel mutations in the ATP2C1 gene.

Hailey-Hailey disease is an autosomal dominant skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. Mutations in ATP2C1, the gene encoding a novel, P-type Ca2+-transport ATPase, were recently found to cause Hailey-Hailey disease. In this study, we used conformation-sensitive gel electrophoresis to screen all 28 translated exons of ATP2C1 in 24 Hailey-Hailey disease families and three sporadic cases with the disorder. We identified 22 different mutations, 18 of which have not previously been reported, in 25 probands. The novel mutations comprise three nonsense, six insertion/deletion, three splice-site, and six missense mutations and are distributed throughout the ATP2C1 gene. Six mutations were found in multiple families investigated here or in our previous study. Haplotype analysis revealed that two of these are recurrent mutations that have not been inherited from a common ancestor. Comparison between genotype and phenotype in 23 families failed to yield any clear correlation between the nature of the mutation and clinical features of Hailey-Hailey disease. The extensive interfamilial and intrafamilial phenotypic variability observed suggests that modifying genes and/or environmental factors may greatly influence the clinical features of this disease.

Calcium-Transporting ATPases↗