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Biomedical subjects

R Girot

Publications and source records attributed to R Girot.

At least 91 records · Page 5Linked to original sources
PubMed1991

[Current trends in hemoglobin genetic diseases].

The current aspects of genetic diseases of hemoglobin are as follows. (1) The localisation and the dimension of at-risk populations for sickle cell disease and thalassemia in metropolitan France are not exactly known. However, some recent epidemiological studies and preliminary results of studies being currently underway allow to delimitate the problem. The at-risk populations are localized in the parisian area, in Provence-Côte d'Azur, in the Lyon and Grenoble areas, in Lorraine, Alsace and the Northern part of France. The number of heterozygotes for these diseases is situated between 250,000 and 350,000. The number of homozygotes born each year is between 100 and 150. More than 250 homozygous thalassemia patients and probably 2,000 to 3,000 sickle cell patients are living at this time in metropolitan France. (2) The transgenic mouse model is an experimental tool which allowed important advances in the knowledge of the hemoglobin human genome. Thus, we now have lines of mice expressing human fetal (g genes) and human adult (b genes) hemoglobins. Recently, enhancer sequences have been identified in 5' to the embryonic gene epsilon. When this region, named locus-region-control (LCR), is inserted along with g and b globin genes, their expression is observed at a very high level. The main objective of this technique is to obtain mouse model for sickle cell disease and thalassemia for studies on the pathophysiology and the therapy of these diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1990

Bone disease in children with homozygous beta-thalassemia.

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.

Adolescent↗
PubMed1990

DNA amplification of HIV-1 in seropositive individuals and in seronegative at-risk individuals.

We assessed the HIV-1 status of seropositive and seronegative at-risk individuals by the polymerase chain reaction. Fifty-four out of 55 HIV-1-seropositive samples scored positive. However, HIV-1 proviral DNA was not detected in 16 seronegative homosexuals, 20 seronegative polytransfused haemophiliacs and 20 seronegative thalassaemic children, 20 individuals with isolated and persistent anti-core antibodies and 74 seronegative blood donors. These data indicate that positive HIV-1 DNA is likely to be an exceptional phenomenon in HIV-seronegative people.

Adult↗
PubMed1990

Absence of HIV DNA sequences in seronegative polytransfused thalassemic patients.

The risk of infection with human immunodeficiency virus (HIV) by transfusion is not totally eliminated, since contaminated blood given before seroconversion to HIV is not detected on the actual biological screening. We used the polymerase chain reaction (PCR) assay (with one primer pair in the gag region and two in the pol region) to detect HIV DNA sequences in 30 seronegative polytransfused thalassemic patients and in 60 seropositive individuals (used as positive controls). We did not observe PCR-positive HIV-antibody-negative results in seronegative polytransfused patients.

Adolescent↗
PubMed1990

Partial splenectomy in homozygous beta thalassaemia.

Partial splenectomy was performed on 30 patients with homozygous beta thalassaemia to reduce blood requirements and to avoid the risk of overwhelming postsplenectomy infections; 24 patients had thalassaemia major and six thalassaemia intermedia. Five patients received a high transfusion regimen before and after surgery and 25 a lower one. Follow up after surgery ranged from one to four years. Partial splenectomy improved the long term haematological state in the six patients with thalassaemia intermedia. Recurrence of hypersplenism occurred in nine of the 24 patients with thalassaemia major, however, and complete splenectomy was required. Serum IgM concentrations were not significantly modified by surgery. The mean (SD) residual spleen after surgery was 4.45 (2.36) cm measured by scintigraphy. No severe infections occurred after surgery; however, most patients were routinely treated with phenoxymethylpenicillin and the protective effect of the remaining spleen could not be exactly determined. Because of the possibility of recurrence of hypersplenism, routine partial splenectomy when splenectomy is needed in thalassaemia major is not advised, except in children under 5 years whose risk of overwhelming postsplenectomy infection is greatest.

Adolescent↗
PubMed1990

Platelet function in sickle cell disease during steady state.

Platelet function was investigated in 37 patients with sickle cell disease during steady state. The measurement of platelet aggregation in whole blood, demonstrating interaction of sickle cells and platelets, showed increased activity in patients compared to controls. In contrast, by classical platelet aggregation in platelet-rich plasma (PRP) we observed decreased platelet aggregation in sickle cell patients. Aggregation of washed platelets appeared identical in patients and controls beta thromboglobulin (beta TG) and platelet factor 4 (PF4) as well as fibrinopeptide A (FPA) plasma levels were increased in patients with sickle cell disease. These results suggest that in sickle cell patients there is in vivo platelet stimulation, which may therefore appear "exhausted" in patients plasma during in vitro studies, and also a possible role of coagulation in the pathophysiology of sickle cell disease as supported by high levels of FPA.

Adenosine Triphosphate↗
PubMed1989

[Treatment of homozygote beta thalassemia in Algiers. A 5-year follow-up of 66 patients].

During the years 1982-1987, 66 patients with homozygous beta-thalassaemia were treated at the blood transfusion centre of Algiers. The patients, aged from 1 to 23 years in 1982, came from 48 families, 30 of which were issued from consanguinous unions. The patients fell into three groups according to the early institution and quality of treatment (blood transfusions, antibiotic therapy, desferrioxamine given when available). The beneficial clinical effects observed (satisfactory growth and development, reduction of splenomegaly and hypersplenism, attenuation of craniofacial malformations, performance at school) seemed to be directly related to the mean haemoglobin level prior to transfusion and to the early institution of treatment. Four patients died of anaemia and haemochromatosis. The incidence of viral contamination was 27.5 per cent for the hepatitis B virus and nil for the human immunodeficiency virus.

Adolescent↗
PubMed1989

[Intermediate homozygous beta-thalassemia with high fetal hemoglobin synthesis. Molecular analysis].

The intermediate character of beta-thalassaemia may be due to a molecular cause capable of reducing the unbalance between alpha and non-alpha chains. We report the case of a child born of consanguineous parents and homozygous for beta-thalassaemia. The patient was irregularly transfused until puberty. His haemoglobin level was around 10 g/dl, and in his erythroid line only foetal haemoglobin was synthesized, except for small amounts of haemoglobin A2. An in vitro study of globin chains biosynthesis confirmed the total absence of beta chains synthesis, and the molecular defect was characterized. This was deletion of a colon 6 nucleotide on both chromosomes, making the messenger RNA unstable and non-traducible. The initial diagnostic approach in this patient included the indirect determination of restriction polymorphism (Orkin's halotype IX), a search for the presence or absence of a nonsense codon 39 often associated with haplotype IX, and the demonstration of a frameshift in the reading phase of codon 6. The very high synthesis of foetal haemoglobin in this patient seems to be linked with a C----T substitution in -158 of the G gamma gene creating an Xmnl site and a gamma phi beta (+-++) subhaplotype which appears to be related in all haemoglobinopathies to an increased synthesis of foetal haemoglobin with predominant G gamma chain.

Adult↗
PubMed1989

Studies of variations of subcutaneously infused desferrioxamine and iron movements in thalassaemia children.

Desferrioxamine (DFO) plus ferrioxamine (FO) variations and alterations in plasma and urinary iron (Fe) levels were investigated in eight children with thalassaemia major during a 12-h s.c. DFO infusion at a dose of 40 mg/kg body weight. During the infusion, blood samples were regularly taken and total urine was also regularly collected in all patients. In the plasma, a mean DFO plus FO plateau level of 9 mg/l was reached after 4 h and remained steady in the subsequent 8 h. At 30 h the mean DFO plus FO concentration in plasma was still 4.5 mg/l. At 30 h, the urinary excretion ranged from 15% to 70% of the infused dose (mean: 42%). In plasma, the Fe concentration increased on average by 20% (range 10%-30%), remained steady during the DFO infusion, then returned to the basal level after 16-24 h. Urinary Fe excretion started early and still persisted 18 h after the infusion. The amount excreted at 30 h ranged from 5 to 27 mg (mean: 13.6 mg). This study emphasizes the delay in obtaining a DFO plus FO plateau in plasma, the important interindividual variations and the slow decrease of the drug after the end of the infusion. It points out the delay and the values of the urinary Fe excretion compared to the plasmatic and urinary drug variations.

Adolescent↗
PubMed1989

[DNA amplification using the polymerase chain reaction method applied to the detection of HIV-1 in seropositive subjects and in seronegative subjects at risk].

Polymerase Chain Reaction (PCR) allows the amplification of specific segments of Human Immunodeficiency Virus (HIV) genome. This technique is of interest for direct detection of HIV-1 DNA sequences in peripheral blood mononuclear cells. In our study, 54 out of 55 HIV-1 seropositive subjects were found positive with PCR assay. No detection of HIV DNA was observed in 36 seronegative at risk subjects (16 homosexuals and 20 polytransfused haemophiliacs), in 20 subjects with isolated and persistent anti-core antibodies, in 20 thalassemic polytransfused children and in 74 HIV seronegative blood donors (negative controls). These results are consistent with those of classical HIV serology and indicate that latent HIV-1 infection in seronegative at risk subjects is not a frequent event, if it exists.

Adult↗
PubMed1989

Use of the ferritin/alanine aspartate transaminase ratio as an iron overload marker independent of liver cell damage.

To define an iron overload index independent of liver cell damage, the mean annual levels of alanine aspartate transaminase (ALAT) and serum ferritin and their ratios were determined. Ferritin/ALAT ratio values were compared between two groups of patients with acute or chronic hepatitis without iron overload, and one group of thalassaemic patients with iron overload. The two groups without iron overload exhibited ferritin/ALAT ratio values of 2 and 1.2 respectively; a ratio value higher than 10 was always observed in those patients with iron overload. The ferritin/ALAT ratio is correlated with the degree of iron overload. This ratio increases in regularly-transfused patients without chelation treatment. It generally remains stable or decreases after initiation of iron chelation therapy. The ferritin/ALAT ratio thus appears useful in the follow-up of patients subjected to a long-term transfusional treatment particularly when acute or chronic liver cell damage may interfere with iron overload by increasing serum ferritin values.

Alanine Transaminase↗
PubMed1989

No evidence for a defect in growth hormone binding to liver membranes in thalassemia major.

To test the hypothesis of a defect in GH-receptor interaction, which could explain the growth failure of thalassemic children, the binding of [125I]human (h) GH to membrane fractions prepared from liver biopsies was studied. Small amounts of liver were obtained from 6 girls and 11 boys with homozygous beta-thalassemia, aged 3-15 yr, all prepubertal, at the time of splenectomy. Specific binding of [125I]hGH ranged from 0.37-5.11% of the added radioactivity/100 micrograms liver membrane protein, with variations in both receptor number and binding affinity. This 14-fold variation in hGH binding to liver membranes of thalassemic children was comparable to that in membrane fractions of livers obtained from normal donors at the time of liver transplant. The binding of insulin to liver membranes from the thalassemic patients ranged from 9.8-17.9% of the added radioactivity/100 micrograms membrane protein and from 2.8-15.0%/100 micrograms membrane protein in the normal donors. Insulin and GH binding to liver membranes did not vary in a consistent way. A 3-fold difference was found in 5'-nucleotidase activity of the membrane fractions. Histological hepatic modifications were assessed with respect to siderosis and fibrosis. No correlation was found between these parameters and GH binding. These results suggest that possible membrane alterations are not the only reason for the variations in hGH binding. All patients had retarded growth, and all but 2 had low plasma insulin-like growth factor I levels. No relationship was found between the level of GH binding to liver membranes and the growth failure. Thus, a defect in GH binding to liver membranes is probably not the cause of the growth retardation of thalassemic children.

Adolescent↗