Biomedical subjects

F Dore

Publications and source records attributed to F Dore.

At least 37 records · Page 2Linked to original sources

PubMed1990

[Diagnosis of hepatic hemangioma with simplified double 99mTc labelling].

The authors report on their experience with liver hemangioma (LH) diagnosis by means of a simplified method--that is, the simultaneous, in vivo, double labelling of liver reticuloendothelial system (RES) and of red blood cells (RBC) by 99mTc. Twenty-eight patients with US diagnosis of suspected LH and 15 controls were examined after sequential iv injection of SnCl2, of 99mTc-mucolloid albumin and, after liver scintigraphy, of 99mTc-pertechnetate to conclude in vivo RBC labelling. All patients underwent CT and, if necessary, CT-guided biopsy. Focal colloid defects filled after RBC labelling were shown in 20/22 patients with unquestionable LH. No colloid defects were shown in 6/28 cases (expansive process). 15/15 controls showed unchanged non-filling defects after double labelling. Finally, the authors point out that, in the diagnosis of LH, sequential double labelling of liver RES and RBC appears to be a quicker scintigraphic technique than conventional ones. Moreover, this technique has the same high specificity and sensitivity as more time-consuming ones.

Adult↗

PubMed1989

The homozygous state of G to A--117A gamma hereditary persistence of fetal hemoglobin.

During a study of Sardinian families with hereditary persistence of fetal hemoglobin (HPFH), two unrelated subjects with unusually elevated Hb F levels were identified. By selective amplification of the A gamma gene promoter and hybridization to synthetic oligonucleotides, we demonstrate that these subjects are homozygous for the -117A gamma G----A substitution that is responsible for a form of nondeletional HPFH. The hemoglobin synthetic pattern of these patients is discussed.

Adult↗

PubMed1989

Thalassemia intermedia resulting from a mild beta-thalassemia mutation.

We investigated the molecular basis for a mild phenotype in a group of patients with beta(+) thalassemia originating from Northern Sardinia by definition of the beta-thalassemia mutation, alpha-globin mapping and beta-globin haplotype determination. In nine patients, we detected the compound heterozygous state for the -87 promoter mutation and the codon 39 nonsense mutation; in one patient, we detected the combination of the codon 39 nonsense mutation and beta(+) IVS-1 nt 6 mutation. These patients were either nontransfusion dependent for survival or became transfusion dependent later. We did not detect the -87 promoter mutation in any of 115 thalassemia major patients originating from the same part of Sardinia, investigated as controls. Heterozygotes for the -87 promoter mutation showed statistically higher hemoglobin (Hb) levels and larger and better hemoglobinized RBCs as compared with heterozygotes for the codon 39 nonsense mutation. From these data, we conclude that the -87 promoter mutation is a mild thalassemia allele, able to produce a phenotype of intermediate severity even in combination with a beta(0)-thalassemia mutant. The coinheritance of alpha-thalassemia or the -++-- 5' subhaplotype in several cases may have contributed to development of the mild clinical picture. Characterization of the beta-thalassemia mutation in combination with alpha-globin mapping and haplotype analysis may allow a better estimate of the probability of a given clinical phenotype, thus permitting more accurate counseling.

Adolescent↗

PubMed1988

A frequent A gamma-hereditary persistence of fetal hemoglobin in northern Sardinia: its molecular basis and hematologic phenotype in heterozygotes and compound heterozygotes with beta-thalassemia.

A survey of hemoglobinopathies in northern Sardinia revealed a high frequency (0.3%) of carriers of a hematologic condition characterized by increased expression of fetal hemoglobin during adult life (hereditary persistence of fetal hemoglobin or HPFH). In spite of a normal hematologic phenotype, the heterozygous carriers for this condition display about 12% HbF, almost exclusively of the A gamma type; compound heterozygotes with beta-thalassemia have 20%-26% HbF and run a very mild clinical course. The sequence analysis of the cloned A gamma gene linked to the HPFH determinant revealed the presence of a G----A substitution at position -117 of the A gamma-globin gene promoter; the same mutation occurs also in Greek HPFH, although associated with different restriction polymorphisms. Another hereditary condition characterized by increased HbF (alpha 2 A gamma 2) level and a mild thalassemia phenotype in Sardinia is associated with the -196C----T substitution in the A gamma-globin gene promoter (Sardinian delta beta-thalassemia). Population studies using oligonucleotides complementary both to the -117 G----A and -196C----T mutations and the corresponding normal sequences confirm the presence of these mutations only in HPFH and delta beta-thalassemia chromosomes and exclude these changes being common DNA polymorphisms.

Female↗

PubMed1988

Homozygous beta zero-39 mutation with thalassemia intermedia in northern Sardinia: clinical, hematological and molecular analysis.

In this study, we investigated the clinical and hematological features and carried out alpha- and beta-globin gene analyses in 11 Sardinian adult beta zero-thalassemia homozygotes from Northern Sardinia who were not transfusion-dependent. Oligonucleotide analysis revealed in nine out of 11 patients the nonsense mutation at codon 39, which was associated either with haplotype II or IX (14/16 and 2/16 chromosomes, respectively). Haplotype II was linked to the A gamma T mutation. The G gamma globin level ranged from 50 to 70%. Four out of nine patients (44%) were heterozygous and 3/9 (33%) homozygous for the rightward deletional type of alpha-thalassemia; two (22%) had the normal alpha-gene complement. Patients who were alpha-thalassemia homozygotes (-alpha/-alpha) showed a more balanced globin chain synthesis ratio. This study confirms that alpha-thalassemia may ameliorate the clinical picture of homozygous beta zero-thalassemia.

Adult↗

PubMed1988

Sardinian G gamma-HPFH: a T----C substitution in a conserved "octamer" sequence in the G gamma-globin promoter.

A survey of hemoglobinopathies in Northern Sardinia allowed the identification of two subjects heterozygous for a new type of G gamma hereditary persistence of fetal hemoglobin (HPFH). The G gamma-globin gene from the HPFH chromosome shows the presence of a T----C substitution 175 nucleotides upstream of the CAP site, adding a new example of single-point mutations occurring in the promoter region of the gamma-globin genes and linked to HPFH phenotypes. In this case the mutation affects the 3' end nucleotide of a conserved octamer sequence known to be present in other regulatory elements of several genes.

Base Sequence↗

PubMed1987

The euglycemic clamp in patients with thalassaemia intermedia.

In order to evaluate the influence of haemosiderosis on the glucose metabolism we studied tissue sensitivity to insulin and the metabolic clearance rate (M.C.R.) of this hormone by means of euglycemic clamp technique using an artificial endocrine pancreas in 8 patients with thalassaemia intermedia and 8 control subjects. During the steady-state of euglycemic-hyperinsulinemic clamp (40 mU/m2/min) plasma insulin values were significantly lower and the insulin M.C.R. was significantly higher in thalassaemic patients compared to the controls. To achieve a comparable steady-state insulin concentration to the controls, we performed for a second time the euglycemic clamp in the thalassaemic patients increasing the insulin infusion rate to 80/mU/m2/min. The insulin M.C.R., the M index and the M/IRIs-s ratio were significantly higher in the thalassaemic patients compared to the controls. These results are indicative of an increased tissue peripheral sensitivity to insulin as well as the metabolic clearance rate of this hormone.

Adult↗

PubMed1986

Polymorphism of foetal haemoglobin in the Sardinian beta +-thalassaemia.

12 thalassaemic patients from Northern Sardinia showing the beta + phenotype were examined by isoelectric focusing and high-performance liquid chromatography techniques for the determination of the variant A gamma T globin chain of the foetal haemoglobin. Two patients (16.7%) were homozygotes for the A gamma T gene variant, 2 (16.7%) were heterozygotes and 8 (66.7%) were homozygotes for the normal A gamma I allele. The A gamma T gene frequency was 0.183, much lower than the observed 0.823 in beta zero homozygosity. These data suggest the presence of at least 2 beta +-thalassaemic chromosomes in Sardinians, one associated with the variant A gamma T allele and one associated with the normal A gamma I. The latter is prevalent among adult patients showing the intermediate form of the thalassaemic disease, which is not transfusion-dependent.

Adolescent↗

PubMed1984

Two patients with interstitial del (14q), one with features of Holt-Oram syndrome. Exclusion mapping of PI (alpha-1-antitrypsin).

Patient no 1, a boy, was carrier of a de novo del (14) (pter- greater than q23::q32- greater than qter). Patient no 2, a boy, had a de novo del (14) (pter- greater than q23::q24.2- greater than qter). Common dysmorphisms included bushy eyebrows, frontal bossing, and micrognathia. Patient no 2 had features of Holt-Oram syndrome, i.e. congenital heart defect and severe ulnar defect. Patient no 1 had congenital heart defect but no typical osseous disorders. The association of Holt-Oram syndrome and del 14q24.1 is stressed. Patient no 1 was heterozygous for Pl (alpha-1-antitrypsin) phenotypes. The gene locus could thus be excluded from q24 and q31, and tentatively assigned to q32.1.

Abnormalities, Multiple↗

PubMed1981

[Applicability of cellulose acetate electrophoresis of globin chains to thalassemia screening].

We considered the possible application of globin chain separation on cellulose acetate strips electrophoresis to thalassemia screening. The method shows good accuracy and reproducibility when compared with the chromatographic method on CM-cellulose. The electrophoretic method could be recommended as the simplest test of hemoglobin biosynthesis in countries where high incidence of thalassemic syndromes occurs.

Chromatography, Ion Exchange↗

PubMed1981

[Chemical composition of fetal hemoglobin in Sardinian newborns].

G gamma:A gamma composition of 54 newborns from Sardinia was determined by electrophoresis on polyacrylamide gels containing urea and Triton X-100. G gamma was present at a concentration of 67% with bimodal distribution (with mean values at 65 and 70% respectively). Concentration higher than 76% was not observed. When Hb F in peripheral blood was below 70%, G gamma:A gamma ratio correlates with Hb F%.

Electrophoresis, Polyacrylamide Gel↗

PubMed1981