Cerebral blood flow and blood viscosity in patients with polycythaemia secondary to hypoxic lung disease.

Blood viscosity, cerebral blood flow (CBF) and cerebral oxygen carriage (CBF X arterial oxygen content) were measured in 12 patients with polycythaemia secondary to hypoxic lung disease. CBF and cerebral oxygen carriage were both significantly higher than in a comparative group of 20 patients with raised packed cell volumes and normal lung function. The patients with secondary polycythaemia then underwent venesection and their mean packed cell volume fell from 0.613 to 0.495. This led to a consistent reduction in blood viscosity, which fell by 44% at a low shear rate (0.67/s) and 33% at a high shear rate (0.91/s). CBF rose by 21% (p less than 0.01), but cerebral oxygen carriage did not significantly increase in the group as a whole. Four of the patients with secondary polycythaemia had complained of episodes of confusion before venesection, which improved considerably once the packed cell volume had been lowered. Headache was relieved in a further two patients and none of the subjects was adversely affected by venesection. It was not possible, however, to show a correlation between symptomatic improvement and an increase in cerebral oxygen carriage.     

Exchange Transfusion with Dextran 40 in Polycythaemia Secondary to Hypoxic Lung Disease

In eight patients with polycythaemia secondary to hypoxic lung disease 10 elective exchange transfusions were performed to reduce red cell mass, packed cell volume (P.C.V.), and whole blood viscosity. The rationale for reducing P.C.V. is discussed. It is concluded that patients with P.C.V. of 60% or over will benefit from exchange transfusion and that most patients with P.C.V. over 50% and true polycythaemia will also benefit. We also confirm that the technique of exchange transfusion is a rapid, safe, and effective method of achieving large venesections and reducing red cell mass.     

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.     

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.     

Iron Metabolism in the Anaemia of Chronic Renal Failure. Effects of Dialysis and of Pareuteral Iron

Serial studies of iron transport in patients on maintenance dialysis showed normal or raised values in almost all subjects and a transient increase soon after the start of dialysis in three. These patients, who were seldom or never transfused, had low serum iron levels and normal iron-binding capacity with low saturation. Iron transport was substantially increased by parenteral iron-dextran treatment. Tracer studies showed good iron utilization, with transport to the marrow rather than to the liver. In these circumstances iron therapy is safe and beneficial, and a useful rise in red cell mass was shown to result from it. The packed cell volume was found to be a valid index of red cell mass in these patients. Red cell loss in the dialysers was insufficient to account for the observed reduction in red cell survival.     

Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.

A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident.     

Histidine for Treatment of Uraemic Anaemia

A group of 28 uraemic patients on dialysis treatment were given daily supplements of histidine by mouth. Plasma amino-acid concentration, plasma iron, serum transferrin, packed cell volume, and reticulocyte count were all measured before and after two months of histidine supplementation. The treatment raised the plasma histidine concentration and at the same time there was a rise in transferrin and iron levels and packed cell volume. Reticulocyte counts fell after two months of histidine supplementation.     

Indications for angiography and surgery in carotid artery disease.

The results of angiographic investigation of 211 patients suffering from transient cerebral ischaemic attacks in the carotid territory have been reviewed. The greatest proportion of patients with carotid stenosis and who were referred for endarterectomy were those with a neck bruit ipsilateral to the affected hemisphere. Ocular involvement (amaurosis fugax) was associated with a still higher prevalence of angiographic abnormality, and carotid occlusion was commonest in this group. The implications for the management of patients with transient ischaemic attacks are discussed.     

Influence of transoesophageal echocardiography on therapy and prognosis in young patients with TIA or ischaemic stroke

Objective. To determine the influence of transoesophageal echocardiography (TEE) on therapy and prognosis in patients with cryptogenic transient ischaemic attack (TIA) or ischaemic stroke under the age of 50 years. Methods and results. We evaluated all patients aged 50 and under who were referred to our university hospital for cryptogenic TIA or ischaemic stroke during the period 1 January 1996 to 31 December 2004. All patients underwent both transthoracic echocardiography (TTE) and TEE. Patients with known pre-existent heart disease, such as atrial fibrillation, were excluded. Eighty-three patients with TIA (22) and ischaemic stroke (61) were enrolled. Mean age was 39±8 years (range 18 to 50). In 30% of the patients TEE detected one or more potential cardioembolic source, compared with 10% for TTE (p=0.003). Standard treatment (aspirin 38 mg daily) was changed in 7% of the patients due to the TEE findings. Complete followup was obtained in 93% with an average of 5±3 years. Twelve recurrences occurred; two out of six patients (33%) with therapy change and ten out of 71 (14%) of the patients without therapy change had a recurrent TIA or ischaemic Stroke. Conclusion. In patients with cryptogenic TIA or ischaemic stroke, TEE is superior to TTE in the detection of a potential cardiac source of embolism. However, findings obtained by TEE only influence the already initiated treatment in a small percentage of patients. The recurrence rate both in the group with and without therapy change is high. (Neth Heart J 2009;17:373–7.)     

Blood viscosity after splenectomy.

Blood viscosity and its contributory factors--namely, plasma viscosity, fibrinogen concentration, packed cell volume, red-cell deformability, and platelet count--were measured in 20 asymptomatic patients after splenectomy and compared with those in controls. Whole-blood viscosity was significantly increased after splenectomy and was associated with increased platelet count and, more importantly, decreased red-cell deformability. Blood viscosity was measured in six patients before and after splenectomy and in each an increase in viscosity occurred that did not occur in patients who underwent laparotomy without splenectomy. these findings suggest that the inclusions and protein complexes within the red cell that are normally removed by the spleen decrease red-cell deformability and lead to an increase in blood viscosity. This may account for the observed increase in deaths from ischaemic heart disease many years after splenectomy.     

Haematological complications in polycythaemia vera and thrombocythaemia patients treated with radiophosphorus (32P).

We have evaluated 230 patients with myeloproliferative disorders treated in the last 15 years with 32P. None of the patients affected by essential thrombocythaemia developed haematological complications. In the larger group of polycythaemia patients (214 subjects) only 38 patients (17 males and 21 females) developed complications. 60.5% of these subjects had a minor complications: 1.8% showed a thrombocytopenia lower than 100.10e9/lt, 2.3% anaemia with Hb lower than 10 g%, 2.6% leukopenia lower than 40.10e9/lt and 2.3% a pancytopenia. All these complications were transient and eventually treated with limited blood transfusions. We could not identify a correlation between the dose used and the development of such complications. We noted only that the occurrence of anaemia, given a similar dose, was more frequent in females. Only 7% of all patients presented a major complication after 32P administration. In this case too, there was no correlation with the dose administered. Myelofibrosis and chronic myeloid leukaemia resulted to be the more frequent complication (9 out of 15) but we could not clarify if they represented a natural evolution of polycythaemia vera or were due to the treatment with 32P. Acute leukaemia developed only in 5 patients and again we could not recognized a correlation with the dose administered. Moreover, the time from the diagnosis of polycythaemia vera the onset of acute leukaemia ranged widely. 32P has a definite effect on the prevention of thrombotic and haemorrhagic complications in polycythaemia patients since it prolongs their life but it also increases the incidence of acute leukaemia.     

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.     

Angiographic appearance of carotid bifurcation in pateints with completed stroke,transient ischaemic attacks,and cerebral tumour.

The angiographic appearance of the carotid bifurcation was compared in groups of patients aged 50-59 suffering from transient ischaemic attacks (40 cases), cerebral infarction with completed stroke (44 cases), and cerebral hemisphere tumour (66 cases). Carotid occlusion was found in 14% of those with infarcts and 5% of those with transient ischaemic attacks. Carotid stenosis was found in 40% of those with ischaemic attacks and 14% of those with infarcts. Minor irregularity of the carotid arterial wall was equally common in all three groups.     

THe dynamics of erythropoiesis inhibition in posttransfusion polycythaemia in the rat

The dynamics of erythropoiesis inhibition as the consequence of polycythaemia induced in rats by four to six transfusions of homologous erythrocytes was studied in detail. It was found, that, in rats with polycythaemia elicited by two transfusions of erythrocytes, erythropoiesis inhibition occurs 67h after the first transfusion and it is most pronounced in the period between 115-187 h. The hemopoietic system is not completely free from the inhibitory influence of polycythaemia up to 283 h after the first transfusion. Maintenance of a state of polycythaemia for 17 days by repeated transfusions strongly and durably inhibits the haemopoietic system. The red blood cell system remained for this whole period under the inhibitory effect.     

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.     

Incidence of stroke in Oxfordshire: first year's experience of a community stroke register.

The Oxfordshire Community Stroke Project is a prospective study of all new cases of stroke and transient ischaemic attack in a defined population of about 103 000 patients registered with 49 general practitioners; every case is assessed by a neurologist and most patients undergo a CT scan or are examined post mortem, or both, to ensure accurate diagnosis. Out of 404 cases registered in the first year, 168 patients had suffered a first stroke, 52 a recurrent stroke, and 41 a transient ischaemic attack; 143 were excluded. Of the 168 patients with their first stroke, 153 (91%) were seen by a neurologist and 149 (89%) had a CT scan or came to necropsy. The pathological diagnosis was cerebral infarction in 127 cases (76%), intracranial haemorrhage in 22 (13%), and unknown in 19 (11%). The estimated yearly incidence of first stroke was 1.95/1000 population (age adjusted to 1981 population of England and Wales).     

Ultrastructure of the Bacteroides nodosus cell envelope layers and surface.

The surface structure and cell envelope layers of various virulent Bacteroides nodosus strains were examined by light microscopy and by electron microscopy by using negative staining, thin-section, and freeze-fracture-etch techniques. Three surface structures were described: pili and a diffuse material, both of which emerged from one or both poles of the bacteria (depending on the stage of growth and division), and large rodlike structures (usually 30 to 40 nm in diameter) associated with a small proportion of the bacterial population. No capsule was detected. The cell envelope consisted of four layers: a plasma membrane, a peptidoglycan layer, an outer membrane, and an outermost additional layer. The additional layer was composed of subunits, generally hexagonally packed with center-to-center spacing of 6 to 7 nm. The outer membrane and plasma membrane freeze-fractured through their hydrophobic regions revealing four fracture faces with features similar to those of other gram-negative bacteria. However, some unusual features were seen on the fracture faces of the outer membrane: large raised ring structure (11 to 12 nm in diameter) on cw 3 at the poles of the bacteria; complementary pits or ring-shaped depressions on cw 2; and small raised ring structures (7 to 8 nm in diameter) all over cw 2.     

Mortality from ischaemic heart disease among patients using anticonvulsive drugs: a case-control study.

Patients who use phenytoin and some other anticonvulsive drugs have been shown to have raised concentrations of plasma high density lipoprotein. As this lipoprotein is known to be inversely associated with the incidence of ischaemic heart disease the causes of death of all patients with epilepsy known to be taking anticonvulsive drugs who died during 1978-80 were studied. Of 1399 deaths of anticonvulsant users, 258 (18.4%) were caused by ischaemic heart disease. This was significantly less (p less than 0.001) than the 382 deaths from ischaemic heart disease (27.3%) observed among paired controls matched for sex, age, and date of death. The total cardiovascular mortality was also lower among patients with epilepsy than among controls (p less than 0.02) despite there being more deaths due to cerebrovascular disease among patients. The difference in mortality from ischaemic heart disease was significant for both sexes and was not accounted for by excess deaths due to any other single cause. Users of phenytoin, carbamazepine, and barbiturates (alone or in combination) showed 29% less mortality due to ischaemic heart disease than respective controls (p less than 0.001).     

Assessment of blood echogenicity as an alternative measure to erythrocyte sedimentation rate.

OBJECTIVE--To determine the relation between erythrocyte sedimentation rate and blood echogenicity and whether measurement of erythrocyte sedimentation rate could be replaced by measurement of blood echogenicity in monitoring acute phase reactions. DESIGN--Simultaneous measurement of echogenicity of flowing blood and erythrocyte sedimentation rate in blood samples and comparison of results. SETTING--A radiological department in a university hospital. SUBJECTS--83 patients with a suspected venous thrombosis and 36 healthy volunteers. MAIN OUTCOME MEASURES--Correlations between the erythrocyte sedimentation rate, packed cell volume, and echogenicity of flowing blood. RESULTS--Blood echogenicity correlated poorly with the packed cell volume, but strongly correlated with the erythrocyte sedimentation rate (when the packed cell volume was within reference limits) (correlation coefficient = 0.73). Blood samples with a greatly raised erythrocyte sedimentation rate were highly echogenic. Only one of the 30 samples with an erythrocyte sedimentation rate below 10 mm in first hour had a higher echogenicity than the least echogenic sample of the 19 with a sedimentation rate above 30 mm in first hour. CONCLUSIONS--Echogenicity of flowing blood correlates with the erythrocyte sedimentation rate and its measurement may compete with conventional methods for evaluating the long term changes in acute phase reactions. Also, it has the added advantage that non-invasive in vivo measurements of blood echogenicity may become possible.     

Deep learning tools and modeling to estimate the temporal expression of cell cycle proteins from 2D still images

Automatic characterization of fluorescent labeling in intact mammalian tissues remains a challenge due to the lack of quantifying techniques capable of segregating densely packed nuclei and intricate tissue patterns. Here, we describe a powerful deep learning-based approach that couples remarkably precise nuclear segmentation with quantitation of fluorescent labeling intensity within segmented nuclei, and then apply it to the analysis of cell cycle dependent protein concentration in mouse tissues using 2D fluorescent still images. First, several existing deep learning-based methods were evaluated to accurately segment nuclei using different imaging modalities with a small training dataset. Next, we developed a deep learning-based approach to identify and measure fluorescent labels within segmented nuclei, and created an ImageJ plugin to allow for efficient manual correction of nuclear segmentation and label identification. Lastly, using fluorescence intensity as a readout for protein concentration, a three-step global estimation method was applied to the characterization of the cell cycle dependent expression of E2F proteins in the developing mouse intestine.