Leg ulcers and hydroxyurea: forty-one cases.

BACKGROUND: Hydroxyurea is an antitumor agent used to treat chronic myeloproliferative disorders. Leg ulcerations have been reported in patients undergoing long-term hydroxyurea therapy for myeloproliferative diseases. To better define this dermatological adverse effect of hydroxyurea therapy and to try to understand the pathophysiological process of this disease, we collected medical information for such patients in a multicenter retrospective study. OBSERVATIONS: Forty-one patients (mean age, 67 years) developed leg ulcerations while undergoing hydroxyurea therapy (mean therapy duration, 5 years). The sex ratio was 1, and there was no underlying vascular disease. Hematologic abnormalities were identified. Complete recovery from the ulcerations occurred quickly after withdrawal of treatment in 33 (80%) of the cases. CONCLUSIONS: This longest-reported series of patients confirms the role of hydroxyurea therapy in the onset of leg ulcerations. Healing or improvement requires cessation of treatment. Cutaneous atrophy and impaired wound healing may explain the relationship between hydroxyurea and leg ulcers. In addition, the megaloblastic erythrocytes resulting from the presence of hydroxyurea may circulate poorly through the capillary network. A prospective study in hematologic centers would be valuable.

Synthetic cDNA encoding the rat AT1a receptor: a useful tool for structure-function relationship analysis.

To carry out systematic structure-function studies of the rat angiotensin II receptors by site directed mutagenesis, or production of chimeric receptors, we have produced a synthetic cDNA coding for the AT1a receptor. The synthetic cDNA is 1101 base pairs long, and contains 49 unique restriction sites that are on the average 23 base pairs apart, allowing replacement of specific restriction fragments by synthetic counterparts containing the desired modified sequence. The total cDNA was assembled in the expression vector pECE. After stable expression in Chinese Hamster Ovary cells, the protein encoded by this synthetic cDNA presents a pharmacological profile and a signal transduction mechanism indistinguishable from the wild type rat AT1a receptor.

[Identification of persons with high risk of venous thrombosis]. / Identification des populations à haut risque de thrombose veineuse.

The aim of identification of patients with high risk of deep venous thrombosis is a selective and more efficiency prophylaxis. Deficiencies of coagulation inhibiting and fibrinolytic proteins are implicated in less than 10% of patients. However there are several clinical situations with an increased risk of thrombosis. Thus the characterization of blood abnormalities as screening tests for the diagnosis of patients at risk is an important goal.

Autosomal dominant polycystic kidney disease with primary hyperaldosteronism.

We report three cases of primary aldosteronism associated with autosomal dominant polycystic kidney disease. The diagnosis of primary hyperaldosteronism was based on the presence of hypokalaemia with excessive urinary potassium excretion and/or the characteristic hormonal changes. Renal function impairment due to autosomal dominant polycystic kidney disease could mask hypokalaemia. The interpretation of adrenal imagery may be hindered by adjacent renal cysts. In one case an adrenal adenoma was detected and surgically removed, with only partial correction of the blood pressure. This could be explained by the persisting underlying autosomal dominant polycystic kidney disease. We conclude that in a hypertensive patient with polycystic kidney disease, extrarenal causes of hypertension may be present.

Molecular basis for antithrombin III type I deficiency: three novel mutations located in exon IV.

Antithrombin III (AT III) type I deficiencies are characterized by a 50% decrease of both immunoreactive and functional protein and carry a high risk of thrombotic complication. We have studied the molecular basis for such deficiencies by asymmetric polymerase chain reaction amplification and direct sequencing of the seven exons and of the intron-exon junction of the AT III gene. Three different mutations were observed in the exon IV: a 4-bp deletion, a 2-bp deletion, and a nucleotide insertion. Each of these mutations results in a frameshift introducing premature stop codons at positions 313, 309, and 232, respectively. These results were confirmed by dot-blot analysis with allele-specific oligonucleotide probes. Furthermore, no mutation was observed in the other six exons. The comparison of the type of mutations observed by our group in six cases of type I deficiencies and in 16 cases of type II heparin binding site variants deficiencies suggests that the former are caused by heterogeneous molecular abnormalities while the latter are caused by recurrent missense mutations.