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Biomedical subjects

A J Keidan

Publications and source records attributed to A J Keidan.

18 recordsLinked to original sources
PubMed1989

Pharmacological modification of oxygen affinity improves deformability of deoxygenated sickle erythrocytes: a possible therapeutic approach to sickle cell disease.

1. The formation of polymerized haemoglobin S in sickle cells is critically dependent on the concentration of deoxygenated haemoglobin so that compounds which increase the oxygen affinity of haemoglobin S are potential anti-sickling agents. 2. BW12C [5-(2-formyl-3-hydroxyphenoxy)pentanoic acid] and BWA589C [4-(2-formyl-3-hydroxyphenoxymethyl)benzoic acid] are aromatic benzaldehydes that cause a dose-dependent left-shift of the oxygen saturation curve of haemoglobin S by stabilization of its oxy-(R)-conformation. 3. A 5 micron pore filtration method, which is highly sensitive to polymerization of haemoglobin S, was used to demonstrate a significant improvement in the deformability of deoxygenated sickle erythrocytes at concentrations (0.75-1.5 mmol/l] of BW12C and BWA589C that are achievable in vivo. Both compounds may therefore be of value for the treatment of sickle cell disease. 4. Filtration of sickle cells through pores of 5 microns diameter is a sensitive technique for evaluating the rheological effects of potential anti-sickling compounds.

Anemia, Sickle Cell↗
PubMed1989

Effect of polymerization tendency on haematological, rheological and clinical parameters in sickle cell anaemia.

The polymerization tendency of sickle haemoglobin was estimated as a function of oxygen saturation in 30 patients with homozygous sickle cell anaemia. The deformability of their erythrocytes was also measured, by initial-flow-rate filtration at 37 degrees C through pores of 5 microns diameter, and clinical severity was assessed using a visual analogue scale. By means of partial correlation analysis, it was found that correlations between haematological, rheological, and clinical parameters in sickle cell anaemia could be explained on the basis of an association of each variable with polymerization tendency. Patients with the greatest tendency to form polymer had the least deformable erythrocytes and perceived their disease to be more severe as judged by the visual analogue scale. Polymer formation also appeared to be a determinant of the number of dense cells which, in turn, determine haemolytic rate and erythrocyte deformability.

Anemia, Sickle Cell↗
PubMed1989

Erythrocyte heterogeneity in sickle cell disease: effect of deoxygenation on intracellular polymer formation and rheology of sub-populations.

Erythrocytes from 12 patients with homozygous sickle cell disease in the steady state were fractionated on a Percoll-Stractan density gradient. Erythrocyte deformability was measured by initial-flow-rate filtration through pores of 5 microns diameter and erythrocyte polymer content was calculated as a function of oxygen saturation. Density fractionated sub-populations of sickle cells showed distinct rheological characteristics, the filterability of dense cells being impaired by minimal oxygen desaturation with the apparent formation of little or no intracellular polymer. Lighter cell fractions required a greater degree of deoxygenation and polymer formation to impair deformability, although this occurred prior to morphological sickling. Dense cells therefore exert a disproportionate effect on blood rheology in sickle cell disease and are likely to have an adverse rheological effect in vivo at arterial oxygen tension.

Anemia, Sickle Cell↗
PubMed1988

Laboratory tests for monitoring prophylactic exchange transfusion in pregnancy complicated by sickle cell disease.

Prophylactic exchange transfusion is of uncertain value in pregnancy complicated by sickle cell disease (SCD), and there is a lack of laboratory tests to monitor its effect and determine the optimal number and frequency of transfusions. In a prospective study of four consecutive pregnancies complicated by SCD, the product of the PCV and percentage of haemoglobin S gave a 'sicklecrit' value that showed a significant (P less than 0.01) improvement following transfusion. Erythrocyte filterability through pores of 5 microns diameter also improved significantly (P less than 0.05) whereas whole blood viscosity did not, owing to the overriding effect of the increase in PCV. Measurement of sicklecrit and erythrocyte filterability, reflecting blood rheology in large and small vessels respectively, may therefore be used to monitor the effects of exchange transfusion in SCD.

Anemia, Sickle Cell↗
PubMed1988

Unexplained lymphadenopathy in sickle cell disease.

Progressive lymphadenopathy in a previously healthy female adult with homozygous sickle cell disease (SCD) was found to be due to infection with the human immunodeficiency virus (HIV). Detailed questioning identified several risk factors for HIV in this apparently low-risk patient. Parenteral therapy and heterosexual relationships while abroad may place such SCD patients at risk of HIV infection and its sequelae. The additional risk due to the underlying immunological abnormalities which have been identified in SCD patients is unclear in the absence of prospective studies or reported cases.

AIDS-Related Complex↗
PubMed1988

Polymerization of sickle cell hemoglobin at arterial oxygen saturation impairs erythrocyte deformability.

We have examined the filterability of sickle erythrocytes, using an initial-flow-rate method, to determine whether sufficient hemoglobin S polymer forms at arterial oxygen saturation to adversely affect erythrocyte deformability. The amount of intracellular polymer was calculated as a function of oxygen saturation to estimate the polymerization tendency for each of eight patients with sickle cell anemia (SCA). Progressive reduction of oxygen tension within the arterial range caused a sudden loss of filterability of SCA erythrocytes through 5-micron-diam pores at a critical PO2 between 110 and 190 mmHg. This loss of filterability occurred at a higher PO2 than did morphological sickling, and the critical PO2 correlated significantly (r = 0.844-0.881, P less than 0.01) with the polymerization tendency for each patient. Study of density-gradient fractionated cells from four SCA patients indicated that the critical PO2 of dense cells was reached when only a small amount of polymer had formed, indicating the influence of this subpopulation on the results obtained for unfractionated cells. Impairment of erythrocyte filterability at high oxygen saturation (greater than 90%) suggests that small changes in oxygen saturation within the arterial circulation cause rheological impairment of sickle cells.

Anemia, Sickle Cell↗
PubMed1987

Oxpentifylline and cetiedil citrate improve deformability of dehydrated sickle cells.

Erythrocytes from 14 patients with homozygous sickle cell anaemia were treated with the calcium ionophore A23187 to induce loss of cellular potassium and water. The dehydrated cells showed a decrease in filterability (loss of deformability) through pores of 5 micron diameter. Oxpentifylline and cetiedil citrate, which preserve erythrocyte cation and water content, had a significant (p less than 0.01) protective effect against loss of deformability at a concentration of 1 mumol/l. Oxpentifylline showed no adverse effect on the rheology, morphology, or haemolysis of sickle cells at concentrations up to 500 mumol/l. Drugs that act on the erythrocyte membrane to maintain cell hydration are of potential rheological benefit in sickle cell anaemia.

Anemia, Sickle Cell↗
PubMed1987

Rheological effects of bed rest in sickle cell disease.

A serial rheological study in two patients with homozygous sickle cell disease whose leg ulcers healed as a consequence of bed rest showed an improvement in erythrocyte deformability (filterability) associated with evidence of decreased haemolysis and a fall in the number of irreversibly sickled cells. This rheological improvement may aid the healing of leg ulcers by increasing blood flow in the ulcer base. The effects of bed rest on the rheology of sickle cell disease should be taken into account in future studies of vaso-occlusive crisis.

Adult↗
PubMed1987

Painful sickle cell crises precipitated by stopping prophylactic exchange transfusions.

A patient with homozygous sickle cell disease showed a reduced incidence of painful crises as a result of regular exchange transfusion, but on three occasions when transfusion treatment was interrupted, a painful crisis occurred. Onset of painful crisis was associated with raised packed cell volume (PCV) or percentage of haemoglobin S (HbS%), or both. Measurement of whole blood viscosity using in vitro mixtures of blood group compatible normal (AA) and sickle (SS) cells showed that above an HbS of 25% any increase in PCV caused a disproportionate increase in whole blood viscosity. These clinical observations and laboratory data suggest that when regular exchange transfusions are terminated both HbS% and PCV should be carefully monitored. Prophylactic venesection should be considered for patients who maintain their PCV after transfusion as HbS% rises.

Adult↗
PubMed1986

Effect of BW12C on oxygen affinity of haemoglobin in sickle-cell disease.

Eight subjects with sickle-cell disease in the symptom-free steady-state received a single one-hour infusion of the new anti-sickling agent BW12C on a total of eleven occasions. A dose-dependent increase in wholeblood oxygen affinity was observed, resulting from the action of BW12C in stabilising the oxy-conformation of haemoglobin and causing a left shift of the oxygen saturation curve. At the highest dose given (20 mg/kg bodyweight), up to 23% of haemoglobin was modified to a BW12C-reacted high-affinity form without evidence of tissue hypoxia. There was biochemical and rheological evidence for a transient decrease in haemolytic rate.

Adult↗
PubMed1986

Infective complications of aplastic anaemia.

Patients with aplastic anaemia have a relatively specific immune defect--leucopenia with neutropenia. We have carried out a retrospective analysis of infective episodes in 11 patients with aplastic anaemia. 5723 follow-up days accrued and 29 infective episodes were documented. Overall the number of infective episodes was significantly associated with the mean white cell and monocyte counts (r = 0.59, 0.02 less than P less than 0.05) but not with length of follow-up, presentation values of white cell, neutrophil and monocyte counts, or mean neutrophil count. The patients appeared to divide clinically into two groups, those at low risk (seven patients) and those high risk (four patients) of infection. Patients in the high risk group had significantly more infections (P = 0.01) and significantly lower monocyte counts (0.02 less than P less than 0.05) than patients in the low risk group. These results are in contrast to similar studies in patients with chemotherapy-induced neutropenia; in our patients the overall rate and severity of infection was low, Gram negative infections were uncommon and monocytopenia appeared to be of greater importance than neutropenia in determining susceptibility to infection.

Adolescent↗