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G Ivaldi

Publications and source records attributed to G Ivaldi.

At least 19 recordsLinked to original sources
PubMed2004

Unreliable estimation of HbA due to the presence of Camperdown haemoglobin [beta 104 (G6) Arg --> Ser].

AIMS: To suggest the possible unreliability of HbA(1c) determination in presence of haemoglobin variants during routine metabolic evaluation. METHODS: We present a case of Camperdown haemoglobin, accidentally detected in a middle-aged Italian man during routine metabolic evaluation for newly diagnosed diabetes. The haemoglobin variant has been identified by exchange high performance liquid chromatography (CE-HPLC) (VARIANT trade mark HbA(1c) Program, Bio-Rad Laboratories, Hercules, CA, USA), and characterized at molecular level by direct sequencing. RESULTS: A 56-year-old male of Northern Italian origin, presented to our centre for a Type 2 diabetes mellitus of recent diagnosis. HbA(1c) determination was routinely determinated. The patient's chromatogram showed an inappropriate peak of 38.5% in the HbA(1c) position suggestive for the presence of abnormal haemoglobin. Further evaluation identified an abnormal haemoglobin peak even higher (49.5%) eluting at 1.34 minutes in P2-window. Molecular characterization of the mutation showed a nucleotide replacement, AGG --> AGC at codon 104, causing the amino acid replacement Arg --> Ser at position 104 (G6) that give rise to Hb Camperdown. CONCLUSIONS: Haemoglobinopathies can lead to inaccurate glycated haemoglobin level determination. In patients carrying haemoglobin variants, the different methods for determinations of glycated haemoglobin could result in different errors, showing either higher or lower values than expected.

Chromatography, High Pressure Liquid↗
PubMed2002

Functional studies on nine different haemoglobins with high oxygen affinity.

Nine carriers of beta-abnormal haemoglobins with increased oxygen affinity (Hb X) were examined. Their oxygen dissociation curves from whole blood were more or less left-shifted, with six of nine also characterized by biphasism. This refers to an 'inflection point' usually positioned at about 50-60% of Hb O(2) saturation, commonly believed to be a limit between oxygenation of the normal and abnormal components. In effect, the inflection does not always correspond to the Hb X level, which sometimes is much lower than 50% of the total Hb. Moreover, the upper half segment of the dissociation curve could not only be an expression of Hb A oxygenation, since it is always left-shifted. However, a high Hb A level is commonly believed to be the main compensatory factor of these subjects, but many indications suggest that often they have at least three, and not only two, main haemoglobin species: Hb A, Hb X plus hybrids of the type alpha(2)beta(A)beta(X). These would oxygenate after Hb X, but before Hb A. Finally, the interaction of 2,3-diphosphoglycerate with Hb X and/or hybrid tetramers must be altered, and the releasing of oxygen from both is more or less reduced. Unfortunately, it is difficult to demonstrate the presence of hybrids directly, i.e. with amino acid analysis of the abnormal beta-globin.

Chromatography, High Pressure Liquid↗
PubMed2001

Charge distribution as a tool to investigate structural details. II. Extension to hydrogen bonds, distorted and hetero-ligand polyhedra.

It is shown that one of the main reasons for most failures of the methods for calculating distance-dependent bond strengths is related to the distortion of the coordination polyhedra. The charge distribution (CD) method which depends on only one universal empirical parameter (contraction parameter) is modified to include: (i) an iterative calculation of the effective coordination number (ECoN), to deal with structures containing very distorted coordination polyhedra; (ii) a specific contraction parameter to treat structures containing any type of hydrogen bond; (iii) scale factors for coordination subshells, to treat structures with hetero-ligand polyhedra. The contraction parameter for the hydrogen bonds was obtained from 119 well refined structures based on neutron diffraction data. Examples of the application of the iterative charge distribution (CD-IT) are presented to show the efficiency of the new method in dealing with distorted (including hydrogen bonding) and hetero-ligand polyhedra. In particular, analysis of a series of 74 structures with pentacoordinated cations shows that deviations from overall trends are related to structure instability. The possible failure of the method with polyionic structures and 'dynamic' structures is discussed.

Journal Article↗
PubMed2001

A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated.

Local recurrences after breast conserving surgery occur mostly in the quadrant harbouring the primary carcinoma. The main objective of postoperative radiotherapy should be the sterilisation of residual cancer cells in the operative area, while irradiation of the whole breast may be avoided. We have developed a new technique of intra-operative radiotherapy (IORT) of a breast quadrant after the removal of the primary carcinoma. A mobile linear accelerator (linac) with a robotic arm is utilised delivering electron beams able to produce energies from 3 to 9 MeV. Through a perspex applicator, the radiation is delivered directly to the mammary gland and to spare the skin from the radiation, the skin margins are stretched out of the radiation field. To protect the thoracic wall, an aluminium-lead disc is placed between the gland and the pectoralis muscle. Different dose levels were tested from 10 to 21 Gy without important side-effects. We estimated that a single fraction of 21 Gy is equivalent to 60 Gy delivered in 30 fractions at 2 Gy/fraction. Seventeen patients received a dose of IORT of 10 to 15 Gy as an anticipated boost to external radiotherapy, while 86 patients received a dose of 17-19-21 Gy intra-operatively as their whole treatment. The follow-up time of the 101 patients varied from 1 to 17 months (mean follow-up time was 8 months). The IORT treatment was very well accepted by all of our patients, either due to the rapidity of the radiation course in cases where IORT was given as the whole treatment or to the shortening of the subsequent external radiotherapy in cases where IORT was given as an anticipated boost. We believe that single dose IORT after breast resection for small mammary carcinomas may be an excellent alternative to the traditional postoperative radiotherapy. However, a longer follow-up is needed for a better evaluation of the possible late side-effects.

Adult↗
PubMed2001

Direct DNA analysis in a new Italian carrier of Hb-Belfast: beta 15 (A12) Trp-->Arg.

A young woman aged 21 was found to be a new carrier of Hb-Belfast: beta 15 (A 12) Trp-->Arg, and the characteristics of her hemoglobinopathy were not different from those of the four cases so far described: mild hemolysis with molecular instability of the abnormal Hb, red cells inclusion bodies, and slight alterations of some functional parameters of whole blood. On this occasion, direct DNA analysis indicated the genomic nucleotide replacement of the disease: TGG-AGG. This was inherited by the mother, originating from Bari (Apulia).

Adult↗
PubMed2000

Inter-method differences and commutability of control materials for HbA2 measurement.

The intermethod variability of control materials and patient blood samples for the measurement of hemoglobin A2 (HbA2) were compared. A set of 54 blood samples and 10 control materials were analyzed in duplicate by HPLC and microcolumn methods. For each set of methods the distances of the materials from the regression line of patient blood results (expressed as normalized residuals) were calculated. Four out of ten controls had normalized residuals exceeding three standard deviations from the regression line. Moreover, total Hb and Hb derivatives analysis proved that only a minority of the controls could be considered similar to patients' blood samples. Intermethod calibration performed "a posteriori" by the two best performing control materials improved intermethod variability among all the five tested methods. We conclude that the use of high resolution HPLC methods together with appropriate commutable control materials allows for better harmonization of results in the field of diagnosis of hemoglobin disorders in research and clinical practice.

Calibration↗
PubMed1998

Hemoglobin Agenogi [beta 90 (F6) Glu-->Lys] found in Piedmont. Case report.

An electrophoretically slow-moving hemoglobin, with abnormal beta chains, has been found in a young woman and in three members of her family. This variant amounted to 41% of the total Hb, and did not cause important clinical manifestations, although characterized by decreased oxygen affinity. Structural and aminoacid analyses revealed the mutation of Hb-Agenogi: 90 (F6) Glu-->Lys, a rare variant so far detected in unrelated racial and ethnic groups. This is the first affected family of ascertained Piedmontese ancestry.

Adult↗
PubMed1997

A new fast-moving variant causing erythrocytosis and mild hemolysis: Hb Gàmbara [beta 82(EF6)Lys-->Glu].

Hb Gàmbara is a new hemoglobin variant with abnormal beta chains that has been found in three out of four members of a family of Lombardy origin (Gàmbara, Brescia, Northern Italy). The affected subjects led a normal life, but they had modest erythrocytosis and mild (compensated) hemolysis with slight splenomegaly. Their abnormal hemoglobin was about 52% of the total hemoglobin, and was shown to be stable by the isopropanol test. Whole blood P50 of the proband was 19.3 Torr, Bohr effect was decreased (-0.25), as well as the molar ratio between the 2,3-diphosphoglycerate level and total hemoglobin of erythrocytes (0.68). The purified abnormal hemoglobin was characterized by an altered oxygen affinity, low n-factor, chloride, and 2,3-diphosphoglycerate effects. The Bohr effect was about 40% of the normal control. The abnormal hemoglobin moved faster than Hb A at alkaline electrophoresis, and split into two fractions, probably due to the formation of hybrid tetramers (alpha 2 beta A beta X). The reversed phase high performance liquid chromatogram from the tryptic digest of the aminoethylated abnormal beta chain subunits indicated the presence of an extra peptide, beta T-9, 10, replacing the individual peptides beta T-9 and beta T-10. Finally, the proband's DNA, drawn from a suitable segment of the beta structural gene (exon 2), revealed a nucleotide sequence carrying the heterozygous mutation AAG-->GAG at codon 82. This led to a Lys-->Glu substitution at position 82(EF6) of the beta chain.

Electrophoresis↗
PubMed1992

Hemoglobin Dallas (alpha 97(G4)Asn-->Lys): functional characterization of a high oxygen affinity natural mutant.

Hemoglobin Dallas, an alpha-chain variant with a substitution of lysine for asparagine at position 97(G4), was found to have increased oxygen affinity (p1/2 = 1 mmHg at pH 7.3 and 20 degrees C), diminished cooperativity (n, the Hill coefficient = 1.7) and reduced Bohr effect (about 50%). Addition of allosteric effectors (such as 2,3-diphosphoglycerate, inositol hexakisphosphate and bezafibrate) led to a decrease in oxygen affinity and increase in cooperative energy. Kinetic studies at pH 7.0 and 20 degrees C revealed that (i), the overall rate of oxygen dissociation is 1.4-fold slower than that for HbA and (ii), the carbon monoxide dissociation rate is unaffected. The abnormal properties of this hemoglobin variant can be attributed to a more 'relaxed' T-state.

Allosteric Regulation↗
PubMed1990

Hb Matera [beta 55(D6)Met----Lys]: a new unstable hemoglobin variant in an Italian family.

Hb Matera is a newly discovered, slow-moving, beta chain variant observed in four members of an Italian family. The variant had a decreased stability in heat and isopropanol tests and numerous red cells contained inclusion bodies. Structural analysis revealed that methionine at position beta 55 was replaced by lysine. Hb Matera's instability is due to an interference in the alpha 1-beta 1 contact of the hemoglobin molecule.

Adult↗
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↗
PubMed1987

Bone marrow transplantation for secondary (therapy-related) acute non-lymphoblastic leukaemia: report of a case associated with adoptive beta-thalassaemia.

A female patient with therapy-related acute non-lymphoblastic leukaemia occurring after intensive combined modality treatment for IIIB Hodgkin's disease was transplanted from her HLA-identical brother. No attempt was made to induce a remission and the transplant was performed with standard chemoradiotherapeutic conditioning. Three years after the transplant the patient is alive in complete remission with a 46,XY karyotype. The donor has a mild, heterozygous beta-thalassaemia ('thalassaemia minima'). The recipient has much more pronounced thalassaemic features, similar to so-called thalassaemia intermedia, with peripheral blood smears indistinguishable from thalassaemia major. The erythrocytic alterations are undoubtedly due to the splenectomy which was performed during a staging procedure, but the marked difference between donor and recipient haemoglobin values cannot be attributed solely to the asplenic state.

Bone Marrow Transplantation↗