Dan Med Bull
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Normal function of the hepatic low-density lipoprotein (LDL) receptor is obligate for normal levels of plasma LDL cholesterol. The LDL receptor regulates the concentration of plasma LDL cholesterol by internalizing apolipoprotein B-100- and apolipoprotein E-containing lipoproteins by receptor-mediated endocytosis. Mutations in the gene encoding the LDL receptor protein give rise to one of the most common classical autosomal dominant inherited disorders in man, familial hypercholesterolemia (FH). ⋯ Familial defective apolipoprotein B (FDB) caused by the R3500Q apolipoprotein B gene mutation may mimic FH but the clinical course, however, is often milder than that seen in patients with LDL receptor gene mutations. A newly discovered third major locus at chromosome 1 may also be of future diagnostic importance although the exact gene remains to be identified. The overall molecular genetic knowledge obtained about FH in Denmark forms the basis for the implementation and use of molecular genetic diagnostics of FH in daily clinical practice.
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Iron is essential for virtually all types of cells and organisms. The significance of the iron for brain function is reflected by the presence of receptors for transferrin on brain capillary endothelial cells. The transport of iron into the brain from the circulation is regulated so that the extraction of iron by brain capillary endothelial cells is low in iron-replete conditions and the reverse when the iron need of the brain is high as in conditions with iron deficiency and during development of the brain. ⋯ After about 20 days of age, iron transport into the brain decreased rapidly, and transferrin receptors appeared on neurons. Iron and transferrin injected into the ventricular system of the developing brain were much more widely distributed in the brain parenchyma than in the adult brain. This high accumulation of substances injected into the ventricles in young animals is probably due to the lower rate of production and turnover of CSF, which will increase the time available for diffusion of proteins into the brain parenchyma, thus giving neurons of the developing brain the opportunity to take up transferrin originating from the CSF.
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Acute liver failure is associated with mortality of around 50%. The aim of the present studies was to examine the circulatory and metabolic state of the splanchnic region in acute liver failure. This had not been studied previously and it could be expected that improved understanding of the pathophysiology of acute liver failure could lead to improved therapy. ⋯ Exchange of ammonia in muscle tissue was studied in 7 patients with acute liver failure and muscle tissue seems to play a major role in ammonia detoxification in acute liver failure. Treatment with high-volume plasmapheresis decreased arterial ammonia, which was likely due to increased urea production or stimulation of glutamine synthesis in muscle tissue. These findings add to our understanding of the pathophysiology and have implications for the management of acute liver failure.
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Politically motivated violence around elections in Zimbabwe has been documented before. A fact-finding mission was planned and undertaken two months ahead of the presidential election March 2002. ⋯ The rule of law, the law points to the deepest disrespect for democratic and human rights in Zimbabwe. Our findings fit into this pattern. Any election under these conditions cannot be free and fair. Health professionals are hindered in exercising their duties both in terms of offering services and in terms of documentation and surveillance of human rights abuses. The international community should monitor the situation in Zimbabwe and strengthen the sanctions if torture systematically is used against opponents of the government or if the food aid is provided selectively to supporters of the government.
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Allogeneic bone marrow transplantation (BMT) is a treatment modality with the potential of curing otherwise lethal diseases. The predominant indications for BMT are haematological malignancies. In BMT alloreactivity plays a pivotal role for the outcome. ⋯ Analyzing all 48 patients the risk of acute GvHD > or = grade II and TRM was significantly higher with HTLp frequencies > 1:100,000 and there was a trend towards a higher risk of relapse with low HTLp frequencies < 1:400,000. Patients in the intermediate HTLp frequency group 1:100,000-1:400,000 had a trend towards improved survival. The HTLp frequency seems to detect clinically significant differences in alloreactivity, that can be useful in donor selection, graft-engineering, T cell add-back and the pharmacological immunosuppression used after BMT.