Isoferritins in acute leukaemia.

Leucocytes containing a high proportion of blast cells were obtained from 11 patients with acute myeloid leukaemia, and leucocytes were also obtained from 2 normal subjects. Ferritin was partially purified from leucocyte extracts and subjected to anion-exchange chromatography and isoelectric focusing. The Fe content of leucocyte ferritin was low, and in all but one case the preparations contained isoferritins corresponding to those found in normal tissues or serum. Only some of the preparations contained the relatively acidic isoferritins which have been described as "carcinofoetal", but which are also present in normal heart and kidney. Ferritin from one patient contained isoferritins of lower isoelectric point than heart ferritin. These results show that there does not appear to be any specific isoelectric focusing pattern for leukaemic cells, and that assays for acidic isoferritins are unlikely to be of use in the diagnosis of leukaemia and in monitoring treatment. However, the very acidic protein found in one preparation suggests that the search for abnormal subunits of ferritin may be fruitful in acute leukaemia

Biological vulnerability to depression: Linked structural and functional brain network findings

Background: Patients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD. Aims: To test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities. Method: A multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recoveredstate patients with MDD with 20 matched healthy controls. Results: The MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus). Conclusions: This is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability

A study into different cell-level cooling strategies for cylindrical lithium-ion cells in automotive applications

Previous research has identified that the ageing rate and performance of lithium-ion cells is negatively influenced by unfavourable cell thermal conditions, specifically, high ambient temperatures and large in-cell temperature gradients. In this paper, the effectiveness of different cell cooling strategies on reducing the in-cell temperature gradient within cylindrical cells is analysed through the development of a 2-D transient bulk layer thermal model displaying anisotropic thermal conductivity. The model is validated against experimental temperature measurements in which the peak error of the simulation was found to be 2% and 5% for the experimental test drive cycle and constant 1C discharge respectively. Results indicate that radial cooling with air or singular tab cooling with liquid may be inadequate in limiting cell temperature gradients to below 5 ℃ for HEV type 32113 cells when subject to 4 loops of the US06 drive cycle

HFE mutations, iron deficiency and overload in 10 500 blood donors

People with genetic haemochromatosis (GH) accumulate iron from excessive dietary absorption. In populations of northern European origin, over 90% of patients are homozygous for the C282Y mutation of the HFE gene. While about 1 in 200 people in the general population have this genotype the proportion who develop clinical haemochromatosis is not known. The influence of HFE genotype on iron status was investigated in 10 556 blood donors. The allele frequencies of the C282Y and H63D mutations were

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

HFE genotype modifies the influence of heme iron intake on iron status

Background: Public health policy to prevent iron deficiency through food fortification or other measures may be disadvantageous to people with hereditary hemochromatosis. Methods: From a cohort of U.K. women, 2531 women were typed for C282Y and H63D mutations in the hemochromatosis gene. These women completed food frequency questionnaires and provided blood for iron status. Results: C282Y homozygotes (n = 31) had serum ferritin concentrations 2.4 times higher (95% confidence interval = 1.9–3.1) than wild types (n = 1774), but heterozygotes (n = 726) were not different from wild types. H63D genotype had no effect on its own. The effect of heme iron intake (from meat, fish, and poultry) was 2.0 times greater (1.2–3.2) on C282Y homozygotes than other groups. Nonheme iron had little effect. Conclusions: There may be scope for dietary intervention in women homozygous for the C282Y mutation. C282Y heterozygotes and H63D homozygotes and heterozygotes have similar serum ferritin concentrations to wild type and need not reduce their meat intake other than as part of a normal healthy diet