Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis

We describe a point mutation creating an additional ATG codon in the 5' untranslated region (UTR) of the HAMP gene, in a patient with juvenile hemochromatosis. By transient in vitro transfection studies, we provide evidence that the additional ATG is functional and prevents normal hepcidin production by inducing an aberrant translation initiation of the pre-hepcidin mRNA

Molecular mechanism of hepcidin deficiency in a patient with juvenile hemochromatosis

We describe a point mutation creating an additional ATG codon in the 5' untranslated region (UTR) of the HAMP gene, in a patient with juvenile hemochromatosis. By transient in vitro transfection studies, we provide evidence that the additional ATG is functional and prevents normal hepcidin production by inducing an aberrant translation initiation of the pre-hepcidin mRNA

Prenatal diagnosis of β-thalassaemia in a twin pregnancy using transabdominal CVS sampling

A 28 year-old Italian woman and her husband were found to be carriers of different alleles of β-thalassaemia. Upon presentation of a twin pregnancy prenatal diagnosis was requested. Sampling of foetal material was performed for each placenta by transabdominal CVS, without any complications for the embryos or the mother resulting from this procedure. The material obtained was used to perform a number of molecular biology tests (sequencing, restriction analysis, ARMS, and dot blot) that allowed the determination and confirmation of the genotype of each embryo: one of the foetuses was heterozygous for the maternal allele β39 C->T and the other one was heterozygous for the paternal allele IVS-1 nt 110 G->A. In this paper we discuss the different options for patients carrying an abnormal foetus in the context of a twin pregnancy as well as ethical and legal implications. We show that transabdominal CVS is a safe and reliable way of obtaining foetal material, and that prenatal diagnosis can be performed using a number of different techniques. Although we agree with selective termination of an abnormal foetus in twin pregnancy, we discuss why this attitude will remain controversial, especially in a central european ethico-legal context

Blood transfusion requirements in otolaryngology - head and neck surgery

Blood requirements for Head and Neck surgical procedures have not been studied carefully. In order to set up an autotransfusion program, the blood loss and transfusion requirements should be known precisely

Effet de l'administration de la r-HuEpo associée a l'hémodilution normovolémique aigüe sur les besoins transfusionnels lors d'interventions pour prothèse totale de hanche

Acute normovolaemic haemodilution (ANH) is used to avoid perioperative blood loss and consists of the withdrawal of whole blood just before or just after anaesthesia induction and its simultaneous replacement by synthetic colloids and crystalloid solutions. In an attempt to improve the efficiency of this technique while at the same time avoiding cardiovascular complications, we set up a pilot study to test the association of rHuEpo/ANH during elective surgery for total hip replacement. Five patients (3 males, 2 females) were included in this study. The amount of whole blood drawn was 3 x 450 ml from the men and 2 x 450 ml from the women. Before blood was taken, the mean increase in haemoglobin was 1.2 +/- 0.9 g/dl and mean increase in reticulocytes 106 +/- 34 G/l. No patient received homologous transfusion during the perioperative period; 3 patients received the totality of predonated blood and one patient 2 of the 3 units taken. The mean fall in haemoglobin at day 1 post-surgery was 3.6 g/dl. In conclusion, the stimulation of erythropoiesis by rHuEpo in the pre-surgery phase led on average to a 1 g/dl gain in haemoglobin, permitting an isovolaemic withdrawal of 900 to 1350 ml of blood depending on body weight without the development of severe anaemia. It was thus possible to perform total hip replacement in all the patients without homologous blood support and with a post-surgery haemoglobin value of > 10 g/dl. This protocol should be further tested in a prospective randomised study (rHuEpo versus placebo) in order to assess the real benefit of rHuEpo

Hautes doses d'immunoglobulines par voie intraveineuse pour le traitement des neutropénies "auto-immunes"

Two patients respectively with acute agranulocytosis and with chronic neutropenia were treated with high-dose immunoglobulins. In the first case, immunologic tests revealed the presence of antigranulocytic autoantibodies: all other tests (antinuclear antibodies, anti-DNA antibodies, immune complexes, latex) were negative. In the second case, all the above mentioned tests were negative. In both patients, neutrophil number returned to normal after the second immunoglobulin injection. Eight months after treatment, the neutrophil count was normal in the first patient and anti-granulocyte tests had become negative. In the second patient there was a late recurrence of neutropenia. The diagnosis of autoimmune neutropenia is difficult to confirm. In the case of peripheral "idiopathic" neutropenia, with infectious complications, high-dose immunoglobulin administration thus appears justified regardless of the results of the immunologic tests. This therapy also has the advantage of avoiding side effects of steroid treatment or of splenectomy