Integration of e-learning resources into a medical school curriculum.

BACKGROUND: E-learning has the potential to make important contributions to medical education, but there has been limited study of a blended approach in which the digital resources are introduced alongside traditional teaching methods such as lectures. METHODS: We describe the successful embedding of an e-learning resource into 3 of the 5 weeks of cardiovascular system teaching for 164 first-year medical students by providing scheduled slots in the timetables. A questionnaire completed by the students at the end of the 5 weeks had a response rate of 66%. Students varied in how they made use of the resource, some systematically working through it and others browsing and studying sections felt to be personally most relevant. RESULTS: Almost all (96%) rated the e-learning resources as probably or definitely of value: they particularly valued interactive activities, animations, video demonstrations, video clips of experts and self-assessment exercises. Graduate students had a significantly more favourable assessment of the e-learning resources than their undergraduate colleagues, while female students felt the value in supporting existing learning opportunities more strongly than male students. CONCLUSIONS: It should not be assumed that all students will choose to use an e-learning resource in the same way and instructional design should enable alternative approaches. The sequence in which the e-learning resource is used in relation to the other learning opportunities, such as lectures and PBL group discussions, may be important and merits further consideration. The experiences reported in this study provide encouragement and pointers for others engaged in the integration of e-learning in their curriculum.

Functional disturbance of marrow stromal microenvironment in the myelodysplastic syndromes.

The potential contribution of abnormal marrow stromal function to ineffective haemopoiesis in the myelodysplastic syndromes is unclear. We have compared the ability of stromal layers from normal (n = 7) and myelodysplastic (n = 9) marrow to alter proliferation and survival of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent cell line F-36P. Co-cultures for 72 h in the absence of exogenous cytokines were either in direct contact with stroma or separated by transwell inserts. On normal stromal layers, the ratio of adherent F-36P cells relative to stromal cells increased from a mean of 0.2 +/- 0.01 (s.d.) at 4 h of co-culture to 0.34 +/- 0.08 after 72 h (n = 7). Corresponding values on myelodysplastic stroma (0.2 +/- 0.02 at 4 h and 0.35 +/- 0.05 at 72 h; n = 9) indicated that the ability of myelodysplastic stromal layers to regulate short-term proliferation of F-36P cells may be similar to normal. Apoptosis of F-36P cells was quantified after co-culture with normal or myelodysplastic stroma: results from myelodysplastic co-cultures were standardized as a fraction of values from co-cultures with paired normal stroma (apoptotic ratio). Augmented apoptosis of F-36P cells was detected in 8/9 co-cultures with myelodysplastic stroma (mean = 15.7 +/- 9.7%, n = 9), compared with corresponding normal stroma (mean = 12.4 +/- 4.6%, n = 7, P < 0.05) with a mean apoptotic ratio of 1.4 +/- 0.5 (P < 0.05). There was no correlation between stroma-related apoptosis and FAB type, tumour necrosis factor-alpha concentrations in the culture supernatant or numbers of stromal macrophages, and no evidence of involvement of the Fas pathway. Increased apoptosis was detected in cells grown in transwell inserts over stroma (23.8 +/- 3%, n = 5) compared to adherent cells in cultures with normal stromal layers, but this survival difference was not observed in co-cultures with myelodysplastic stroma. These results suggest that abnormal stromal function in patients with myelodysplastic syndromes may contribute to increased apoptosis of haemopoietic cells within the marrow microenvironment. The effect appears to be dependent on close cellular contact, rather than the release of soluble factors, but the exact mechanism remains unclear.

Simple assay for urinary iron after desferrioxamine therapy.

A simple method for measuring urinary iron following the administration of desferrioxamine (DF) is described. Ferrioxamine iron is reduced by a reagent containing thioglycolic, hydrochloric, and trichloroacetic acids; the latter ensuring precipitation of any protein present in occasional urines. The iron is measured spectrophotometrically using bathophenanthroline sulfonate. Results are indistinguishable from those obtained using a much more time-consuming preliminary acid digestion, except that in baseline samples the very small amount of spontaneous iron excretion is underestimated. The method is suitable for routine use in monitoring DF therapy.

Studies of erythroblast function in congenital dyserythropoietic anaemia, type I: evidence of impaired DNA, RNA, and protein synthesis and unbalanced globin chain synthesis in ultrastructurally abnormal cells.

Two patients with congenital dyserythropoietic anaemia, type I (CDA) were studied. Their blood reticulocytes showed unbalanced globin chain synthesis with increased alpha:beta globin chain synthesis ratios. A high proportion of the erythroblasts displayed the characteristic "Swiss cheese" abnormality of the nuclear chromatin and some also showed cytoplasmic intrusions lined with nuclear membrane within the nucleus. Occasional erythroblast profiles contained intracytoplasmic inclusions that were ultrastructurally indistinguishable from precipitated alpha chains. The technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography showed gross abnormalities of proliferation in the early polychromatic erythroblasts. The proliferative abnormalities included an arrest of DNA synthesis after the progress of cells through part of the S phase and the formation of several mononucleate and binucleate cells with hypertetraploid total DNA contents. The bone marrow cells gave a normal deoxyuridine suppressed value, indicating that there was no impairment of the methylation of deoxyuridylate. Electron microscope autoradiographic studies showed that a high proportion of the erythroblasts with the "Swiss cheese" nuclear abnormality suffered from a severe impairment, or arrest of DNA, RNA, and protein synthesis.

Quantitative measurement of faecal blood loss: comparison of radioisotopic and chemical analyses.

Blood loss in faeces was assessed by three different methods in five patients with recurrent iron deficiency. In short term (12 day) studies chemical analysis of complete stool collections for haemderived porphyrins (HemoQuant) gave results closely correlated with those obtained by measuring stool loss of 51Cr-labelled red blood cells. Whole body counting for 59Fe was relatively insensitive to small blood losses but allowed losses to be followed up over longer periods. Chemical analysis of faecal porphyrins thus provides a satisfactory alternative to radioisotopic techniques in short term quantitation of faecal blood loss, while longer term whole body counting of 59Fe may still be appropriate in a few patients for the detection and quantification of intermittent blood losses.

Iron chelation studies using desferrioxamine and the potential oral chelator, 1,2-dimethyl-3-hydroxypyrid-4-one, in normal and iron loaded rats.

A novel iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one, and desferrioxamine were compared for their ability to remove iron and for their site of action in iron release in rats. Repeated intraperitoneal injections of the chelators in rats with widespread tissue labelling by 59Fe derived from transferrin showed comparable 59Fe mobilisation by each chelator in normal and iron loaded rats. Specific labelling of a chelatable "cold" iron pool in hepatocytes by 59Fe derived from ferritin showed this pool to be equally accessible to parenteral doses of both chelators and also to oral 1,2-dimethyl-3-hydroxypyrid-4-one, which is an effective oral iron chelating agent that removes iron from parenchymal cells. This and other alpha-ketohydroxypyridines need further development as potential therapeutic agents in human iron overload.

Development of a multiplex ARMS test for mutations in the HFE gene associated with hereditary haemochromatosis.

Genetic testing for hereditary haemochromatosis is likely to be a significant workload for diagnostic laboratories. The C282Y and H63D mutations in the HFE gene associated with hereditary haemochromatosis have previously been detected using a number of methods including alterations in the restriction digest pattern of polymerase chain reaction (PCR) amplified products. An amplification refractory mutation system (ARMS) has been developed that will simultaneously detect both hereditary haemochromatosis mutations. Comparison of the results obtained from the analysis of 46 samples referred for hereditary haemochromatosis testing showed no discrepancies between ARMS and restriction enzyme digestion. Furthermore, consistent results were obtained by ARMS from both blood and buccal mouthwash samples. The ARMS test is quicker and less expensive in terms of consumables and scientist time than restriction enzyme analysis, and is therefore suited to the routine diagnostic analysis of hereditary haemochromatosis.

Management of iron deficiency in renal anemia: guidelines for the optimal therapeutic approach in erythropoietin-treated patients.

Much progress has been made in recent years in the management of anemia associated with chronic and renal failure with recombinant human erythropoietin (r-Hu EPO). However, there remains much debate surrounding the diagnosis and treatment of iron deficiency. To ensure that full benefit from erythropoietin therapy is received, most patients require iron supplement during treatment. There are, however, few guidelines for the use of iron therapy. Iron deficiency results in an inadequate response to r-Hu EPO and is the main cause of resistance to this treatment. Oral iron therapy is of limited value in patients receiving r-Hu EPO. Thus, intravenous iron supplementation should be administered only in patients who do not tolerate available intravenous iron preparations or who are on continuous ambulatory peritoneal dialysis with no evidence of functional iron deficiency. This article provides guidelines for the diagnosis of absolute or functional iron deficiency in patients with renal anemia and suggests treatment schedules for intravenous iron supplementation. We hope that all dialysis patients will be able on this basis to achieve a satisfactory iron status and benefit fully from r-Hu EPO therapy.

Portfolio assessment in medical students' final examinations.

The introduction of an outcome-based approach to education at Dundee Medical School in Scotland instigated a search for assessment methods that would appropriately assess the students' achievements in terms of the learning outcomes. Portfolio assessment has been developed for this purpose and has been adopted for the summative assessment of students in their final examination in Dundee. The contents of the portfolio and the assessment process have been defined and the first cohort of students to be assessed in this way has been studied. The evaluation of the approach demonstrated strong staff support. Students were also positive although with some reservations. It is concluded that portfolio assessment is a powerful approach to assessing a range of curriculum outcomes not easily assessed by other methods and is worthy of inclusion in the assessor's toolkit.

AMEE Medical Education Guide No. 24: Portfolios as a method of student assessment.

This guide is intended to inform medical teachers about the use of portfolios for student assessment. It provides a background to the topic, reviews the range of assessment purposes for which portfolios have been used, identifies possible portfolio contents and outlines the advantages of portfolio assessment with particular focus on assessing professionalism. The experience of one medical school, the University of Dundee, is presented as a case study. The current state of understanding of the technical, psychometric issues relating to portfolio assessment is clarified. The final part of the paper provides a practical guide for those wishing to design and implement portfolio assessment in their own institutions. Five steps in the portfolio assessment process are identified: documentation, reflection, evaluation, defence and decision. It is concluded that portfolio assessment is an important addition to the assessor's toolkit. Reasons for using portfolios for assessment purposes include the impact that they have in driving student learning and their ability to measure outcomes such as professionalism that are difficult to assess using traditional methods.

Quality assurance for point-of-care testing of oral anticoagulation: a large-scale evaluation of the Hemochron Junior Signature Microcoagulation System.

We report the first large-scale evaluation of the Hemochron Junior Signature (HJS) Microcoagulation System for community monitoring of oral anticoagulation and establishment of a programme of internal and external quality assurance. Over 1600 HJS results, with a simultaneous venous sample for central analysis, were obtained over a 19 month period. Monitoring of an initial period of HJS results (n = 135) revealed an International Normalized Ratio (INR) over estimation (mean +1.05), with only 27% of results within 0.5 of the central laboratory INR. A correction factor was introduced which reduced the INR bias to +0.07 and improved the percentage of results within 0.5 of the central laboratory INR to 76% (n = 353). A revised correction factor was later introduced to adjust for an under estimation at higher INR values. This changed the INR bias to -0.05, with 76% of results within 0.5 of the central laboratory INR (n = 1174). Local external quality assurance samples were distributed monthly with a total of 791 samples during the study period. 84% of test results were within 15% of the median value (range 73-97% per month). These results emphasize the value of a robust quality assurance programme when using point-of-care devices for community monitoring of oral anticoagulation.

Iron overload and iron chelation therapy in thalassaemia and sickle cell haemoglobinopathies.

This paper reviews the factors governing the rate of iron loading and iron toxicity in the thalassaemia syndromes and sickle cell disease. It outlines the main determinants of iron mobilization by the iron-chelating drug, desferrioxamine, together with the effects of this drug in clinical practice.

Desferrioxamine-induced iron excretion in humans.

Iron excretion in response to DF in humans is dependent upon the degree of iron overload, particularly of parenchymal liver cells. However, a number of variables, including ascorbate status, erythroid activity and liver disease, affect both the amount of iron mobilized and the route by which it is excreted. Faecal iron, derived from the bile, appears to arise from intracellular chelation of a transit iron pool related to hepatocyte iron stores, whereas urine iron may be derived from iron capable of exchanging with plasma transferrin at cell membranes of both hepatocytes and macrophages. Faecal iron predominates as iron stores return towards normal on regular chelation therapy. An understanding of the variables which influence iron excretion allows rational planning of long-term therapy with DF in patients with iron-loading anaemias. In young children a dose of 40-50 mg/kg given on five or six nights a week from the age of about 3 years is appropriate for prevention of serious iron loading. In older children the dose must be carefully tailored (by means of an individual urinary iron excretion dose-response curve) to achieve maximum safe chelation of pre-existing iron stores. In patients with slower rates of iron loading from excessive gastrointestinal iron absorption, intermittent use of DF infusions may be sufficient to maintain normal iron stores.

Erythrokinetics and iron status in heterozygous beta thalassaemia, and the effect of interaction with alpha thalassaemia.

Ferrokinetic studies, alpha globin gene mapping, and assessment of iron status have been carried out in 16 healthy subjects with heterozygous beta thalassaemia. Six subjects had coinherited alpha thalassaemia and had more balanced alpha/beta globin chain synthesis ratios than the remaining 10 subjects with uncomplicated heterozygous beta thalassaemia. The overall efficiency of erythropoiesis was significantly reduced in the latter group (mean 76 +/- 17 (SD)% of normal), but was indistinguishable from normal in subjects with coexistent alpha thalassaemia. Red cell survival was unimpaired in both groups, indicating that the defect was one of mild ineffective erythropoiesis rather than peripheral haemolysis. Values for total plasma iron turnover were normal or only slightly increased. This suggests a lack of any additional stimulus to erythropoiesis, which might normally be expected to compensate easily for the mild degree of anaemia. Uncomplicated heterozygous beta thalassaemia produces an extremely mild disorder of erythropoiesis, which is dependent on the imbalance between alpha and beta globin chain synthesis, and is not associated with a risk of serious iron overload.

Iron absorption in non-transfused iron loading anaemias: prediction of risk for iron loading, and response to iron chelation treatment, in beta thalassaemia intermedia and congenital sideroblastic anaemias.

A variable rate of iron loading, reaching toxic levels in some patients, was seen in a series of non-transfused patients with beta thalassaemia intermedia or sideroblastic anaemia. The degree of anaemia was a poor guide to the risk of iron overload. However the extent of erythroid hyperplasia, judged by ferrokinetic studies or more simply by bone marrow aspiration, was useful in predicting both the rate of iron loading and the need for iron chelation therapy.

Multiple myeloma and chronic myelomonocytic leukaemia developing in a patient with autoimmune disease.

A 64-year-old lady with a personal and family history of autoimmune disease developed chronic myelomonocytic leukaemia and multiple myeloma simultaneously. Her sister died of acute myelomonocytic leukaemia, but showed no evidence of autoimmune disease. It is possible that chronic immunological stimulation, perhaps by an autoantigen, may predispose toward malignant transformation in both plasma cell and monocyte series. However, the present observations raise the alternative possibility of a primary disorder of monocytes that predisposes toward both autoimmune disease and a clonal disorder of plasma cells.