Intravenous Urea in Treatment of Bone-Pain Crises of Sickle-Cell Disease

Opio, E.; Barnes, P.M.

doi:10.1016/s0140-6736(72)91329-3

Cited by 22 publications

(5 citation statements)

References 4 publications

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“…Thc original clinical trials of both oral and intravenous urea were inconsistent, probably because adcquate controls were lacking. Recently, sevcral controlled trials using urca either orally (Lubin & Oski, 1972) or intravenously for crises (Opio & Barnes, 1972;Kraus et d, 1974;McCurdy et al, 1974) have been reported, and these in fact show no useful clinical effect.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Urea on Sickling

May

Huehns

1975

Br J Haematol

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The effect of urea on the oxygen affinity of sickle cells and normal cells was studied up to a concentration of about 1.0 M. Besides the increase in oxygen affinity found in both normal and sickle cells there was a further increase found only in the sickle cells. This specific increase was caused by the direct inhibition of the polymerization of deoxygenated Hb-S by the urea and was used to measure the extent of this inhibition. Even at concentrations of 1.0 M the urea did not fully inhibit the polymerization. At the urea concentrations recommended for treatment of sickle cell crises and for the oral treatment of the disease there was only a very slight inhibition of polymerization. The small increase in oxygen affinity brought about by these concentrations of urea (equivalent to a log P50 change of 0.016) will cause some additional minimal inhibition of sickling at physiological partial pressures of oxygen. Oxygen dissociation measurements of Hb-A in dilute solution showed that 0.95 M urea had no effect on the interaction of 2,3-DPG and chloride with haemoglobin nor on the haem-haem interactions. This implies that the quaternary 'deoxy' form of the haemoglobin may still form and that the action of urea in inhibiting the polymerization is through interference with the intermolecular bonds rather than by inducing a conformational change which disrupts the bonding. Unless urea at the concentrations recommended for treatment inhibits the sickling of the cells by some mechanism other than its effect on the haemoglobin (such as by an effect on the membrane), these results suggest that it is of little use for the treatment of sickle cell disease.

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Section: Discussionmentioning

confidence: 99%

The Effect of Urea on Sickling

May

Huehns

1975

Br J Haematol

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“…The rationale for the clinical use of urea (prevention of the formation of the hydrophobic bond peculiar to deoxyhemoglobin S) has not been borne out by the trials reported to date (14). The formation of cyanate in urea solutions and the potential reactivity of cyanate with functional groups of proteins (I5), which prompted us to investigate the possible role of cyanate as an inhibitor of red-cell sickling, has been the main stimulus for our studies (1 1).…”

Section: Effects Of Cyanate On the Solubility Of Deoxyhemoglobin S Anmentioning

confidence: 99%

Biochemical and Physiological Properties of Carbamylated Hemoglobin S

Manning¹,

Cerami²,

Gillette³

et al. 1974

Advances in Enzymology - And Related Areas of Molecular Biology

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“…Thus, in many crises, there is likely to be an obligatory painful period which may partially mask a beneficial effect of the agent under trial. The period of treatment and of clinical evaluation should therefore be long enough to allow for this and trials of three hours' duration (Opio and Barnes, 1972) would not seem to be adequate.…”

Section: Clinical Trials In the Established Crisismentioning

confidence: 99%

“…The duration of symptoms before commencing therapy should also be taken into account, and, ideally, the patient should be assessed hourly for the first few hours following admission in order to establish a baseline before specific anti-sickling therapy is initiated (Opio and Barnes, 1972).…”

Section: Clinical Trials In the Established Crisismentioning

confidence: 99%

Management of sickle-cell disease

Stuart¹

1974

Journal of Clinical Pathology

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Intravenous Urea in Treatment of Bone-Pain Crises of Sickle-Cell Disease

Cited by 22 publications

References 4 publications

The Effect of Urea on Sickling

The Effect of Urea on Sickling

Biochemical and Physiological Properties of Carbamylated Hemoglobin S

Management of sickle-cell disease

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