Intermittent hypoxia in patients with unexplained polycythaemia.

The aetiology of polycythaemia is unclear in up to 30% of patients. Twenty patients with unexplained polycythaemia were investigated to see whether they had an intermittent hypoxic stimulus to erythropoiesis that was undetected by conventional investigations for hypoxic secondary polycythaemia. Overnight polygraphic sleep studies showed that five patients had prolonged nocturnal hypoxaemia. Their arterial oxygen saturation was below 92%, the level at which appreciable hypoxic stimulation of erythropoiesis occurs, for 26-68% of the time for which they were studied. Considerable evidence is accumulating that intermittent hypoxia is a potent stimulus to erythropoiesis, and clinicians should consider the possibility of nocturnal hypoxia in patients with unexplained polycythaemia. Appropriate investigation will lead to the correct diagnosis of polycythaemia secondary to hypoxia in some cases previously regarded as idiopathic, and treatment may then be planned accordingly.     

Erythrapheresis in patients with polycythaemia secondary to hypoxic lung disease.

Erythrapheresis was performed in 10 patients with polycythaemia secondary to hypoxic lung disease (mean PaO2, 6.8 kPa (51 mm Hg)). The mean packed cell volume decreased from 0.64 to 0.48 in men and from 0.56 to 0.42 in women, with significant decreases in blood viscosity at both high and low shear rates (p less than 0.001). Patients showed significant improvement in six-minute walking distances (p less than 0.001) and in tests of mental alertness (p less than 0.01) compared to control subjects. Visual analogue scales confirmed symptomatic improvement after erythrapheresis. Erythrapheresis significantly improved symptoms, mental function, and work performance in patients with polycythaemia secondary to hypoxic lung disease. The procedure was well tolerated by all patients and no complications occurred.     

Calculation of standard atomic volumes for RNA and comparison with proteins: RNA is packed more tightly

Traditionally, for biomolecular packing calculations research has focused on proteins. Besides proteins, RNA is the other large biomolecule that has tertiary structure interactions and complex packing. No one has yet quantitatively investigated RNA packing or compared its packing to that of proteins because, until recently, there were no large RNA structures. Here we address this question in detail, using Voronoi volume calculations on a set of high-resolution RNA crystal structures. We do a careful parameterization, taking into account many factors such as atomic radii, crystal packing, structural complexity, solvent, and associated protein to obtain a self-consistent, universal set of volumes that can be applied to both RNA and protein. We report this set of volumes, which we call the NucProt parameter set. Our measured values are consistent across the many different RNA structures and packing environments. When common atom types are compared between proteins and RNA, nine of 12 types show that RNA has a smaller volume and packs more tightly than protein, suggesting that close-packing may be as important for the folding of RNAs as it is for proteins. Moreover, calculated partial specific volumes show that RNA bases pack more densely than corresponding aromatic residues from proteins. Finally, we find that RNA bases have similar packing volumes to DNA bases, despite the absence of tertiary contacts in DNA. Programs, parameter sets and raw data are available online at.     

Electrocardiographic abnormalities associated with raised intracranial pressure.

Serial electrocardiographic (E.C.G.) recordings were taken in seven patients suffering from intracranial conditions, for which their intracranial pressure was directly and continuously monitored with a Konigsberg extradural transducer. The E.C.G. changes observed in patients with raised intracranial pressure were prominent U waves, ST-T segment changes, notched T waves, and shortening and prolongation of Q-T intervals. Two patients with normal intracranial pressure showed no E.C.G. abnormalities but also establish a relationship between E.C.G. abnormalities and changing intracranial pressure.     

Pruritus and severe iron deficiency in polycythaemia vera.

Six patients diagnosed as having polycythaemia vera had severe pruritus that persisted despite adequate haematological control. Iron supplementation was given when iron deficiency was noted in all six patients. The pruritus began to improve two to 10 days after the start of treatment and had completely disappeared after two to three weeks. In three patients the iron treatment was stopped because of unacceptably high haemoglobin concentrations; the pruritus recurred. Since chronic iron treatment may result in increases in red cell mass indiscriminate use of iron in patients with polycythaemia vera and pruritus is not advocated. Nevertheless, in patients with severe symptoms and evidence of iron deficiency treatment with iron, continuing for two to three weeks after the symptoms have abated, may be beneficial.     

Changes in erythropoiesis during the course of polycythaemia vera.

Using 58Fe, 51Cr and cytological parameters, the authors have examined erythropoiesis in 44 polycythaemia vera patients diagnosed as such on the basis of the usual parameters (exept for determination of the erythropoietin level). In the patients divided into four types the following characteristica were observed. In type I, increased erythropoiesis is evident by accelerated plasma iron clearance, greater PIT and EIT as well as enhanced iron utilization and production indices. In type II, in addition to the former signs of increased erythropoiesis moderately shortened red cell life-span and hyposideraemia characteristic of splenic sequestration and resulting from bleeding and blood letting seem to be accompanied by microcytosis. There is a metaplastic erythropoiesis in type III, bone marrow activity decreases, but the increased erythropoiesis is indicated by several parameters already observed earlier. At the time the iron utilization indicative of effective erythropoiesis is decreased, thus ineffective erythropoiesis and considerably shortened red cell life-span are responsible for the enhanced iron turnover. This is also shown by the regression calculations. In type IV effective erythropoiesis was considerably decreased in the patients with severe anaemia. Sings which are indicative of metaplastic erythropoiesis are absent. In one of the patients the morphological changes characteristic of dyserythropoiesis were found. Although all our patients were given treatment. We believe that these alterations in the character of erythropoiesis are not likely to be the consequences of therapy.     

Effect of venesection on calf blood flow in polycythaemia.

Calf blood flow at rest and during postocclusive reactive hyperaemia was measured using an electrocardiogram-triggered plethysmograph in 14 patients with polycythaemia (nine with primary disease and five with polycythaemia secondary to cyanotic heart disease) before and after a course of venesection. The mean packed cell volume was reduced from 0.57 to 0.47, and whole-blood viscosity fell by 50% at low shear rates. Venesection did not affect rest flow, but peak flow was increased by 18%. The increase in peak flow failed to compensate for the reduced haemoglobin content of the blood, calculated haemoglobin delivery being reduced by 23% at rest and 10% during reactive hyperaemia. These results indicate that while venesection improves blood viscosity, this does not necessarily lead to improved delivery of oxygen to the tissues.     

Vascular mural cells in healing canine myocardial infarcts.

Angiogenesis is a critical process in healing of myocardial infarcts, leading to the formation of highly vascular granulation tissue. However, effective cardiac repair depends on mechanisms that inhibit the angiogenic process after a mature scar is formed, preventing inappropriate expansion of the fibrotic process. Using a canine model of reperfused myocardial infarction, we demonstrated that maturation of the infarct leads to the formation of neovessels, with a thick muscular coat, that demonstrate distinct morphological characteristics. Many of these "neoarterioles" lack a defined internal elastic lamina and demonstrate irregular deposits of extracellular matrix in the media. Vascular mural cells in healing infarcts undergo phenotypic changes, showing minimal expression of desmin during the proliferative phase (1 hr occlusion/7 days reperfusion) but in the mature scar (8 weeks reperfusion) acquire a phenotype similar to that of vascular smooth muscle cells in control areas. Non-muscle myosin heavy chains A and B are induced in infarct endothelial cells and myofibroblasts, respectively, but are not expressed in neovascular mural cells. Recruitment of a muscular coat and formation of neoarterioles in mature scars may inhibit endothelial cell proliferation and vascular sprouting, stabilizing the infarct vasculature.     

On the statistical distribution of volumes of cell nuclei and on the dependence of volumes of cell nuclei and DNA amounts in the cell nuclei

Conclusion Based on the simplified model of the cell nucleus it has been shown that (V) is Gaussian. It follows also from this model the independence ofX andV. A number of further reasons for independence ofX andV is shown too.     

Anomalous changes in forward scatter of lymphocytes with loosely packed membranes.

BACKGROUND: Forward scatter (FSC) is generally associated with cell size and has been suggested as a way to differentiate apoptotic from viable cells. Among spleen cells cultured for 48 h, a population of cells (population B) was found to have decreased forward and increased side scatter relative to freshly purified cells (population A). Interestingly, population B was not present early in analysis; this report explores the change in FSC of population B. METHODS: Using a Coulter (Hialeah, FL) Epics Elite ESP flow cytometer, changes in forward scatter and lipid packing of spleen cells were measured. RESULTS: Over time, the FSC of unfixed cells in population B increased from that of the debris field, to reach a stable value by 30 sec (population A's FSC remained constant). When fixed, populations A and B exhibited constant FSC. Population B cells displayed altered lipid packing as reported by MC540, and the FSC changes were mimicked by Nonidet P-40 treatment of freshly purified spleen cells. CONCLUSIONS: Data emphasize the importance of delaying measurements on unfixed cells until FSC readings have stabilized, and suggest that flow cytometry may be a useful tool in studying lipid packing.     

A rheological study of packed red blood cell suspensions with an oscillating ball microrheometer

Rheological properties of concentrated red blood cell suspensions are studied with a magneto acoustic microrheometer in which a ball is suspended in a vertically oriented cylindrical tube. The rheometer uses a conventional falling ball technique to measure steady state viscosity and a vertically oscillating, magnetically driven ball for viscoelastic measurements. The motion of the ball is tracked by ultrasound echo location in which sound waves are transmitted and received by an ultrasound transducer mounted at the base of the tube. The compact size of the rheometer allows rheological studies to be made with microliter quantities of opaque suspensions and permits sudden and accurate changes in temperature. Also, values for the adiabatic compressibility are evaluated from measurements of the speed of sound.     

Moderately raised blood lead levels in children.

There is no doubt that high blood lead levels are associated with mental subnormality and hyperactivity. Several recent studies in Britain and America have investigated the relation between moderate levels, i.e. between 20 and 40 microgram/100 ml and behavioural and cognitive phenomena. Epidemiological studies have generally failed to point to a clearcut relation between such levels and overactivity or decrements in performance on standard intelligence and educational tests. Published studies with the use of chelation techniques have suffered from methodological weaknesses. It is known that socio-economic factors are powerfully related to measured intelligence and behaviour and, on the evidence available, it is to them that attention should primarily be given if preventative measures are being considered. There remains the possibility that more refined test measures would detect impaired functioning in children with moderately raised lead levels, and that there is an interaction effect between lead and host resistance.