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Biomedical subjects

H Tamary

Publications and source records attributed to H Tamary.

At least 37 records · Page 2Linked to original sources
PubMed1997

Neonatal manifestations of congenital dyserythropoietic anemia type I.

Congenital dyserythropoietic anemia type I is a rare inherited bone marrow disorder characterised by macrocytic anemia with pathognomonic morphological ultrastructural features in erythroid precursors. The disease is usually not diagnosed in the neonatal period. In a retrospective study of 31 patients we found that 17 were first seen in the neonatal age with significant anemia (birth hematocrit 0.34 +/- 0.07); 14 of the 17 infants also had early jaundice. Six infants were small for gestational age and two had syndactyly. Although rare, congenital dyserythropoietic anemia type I should be considered in the differential diagnosis of neonatal anemia.

Anemia, Dyserythropoietic, Congenital↗
PubMed1997

Molecular analysis of a compound heterozygote for hypoprothrombinemia and dysprothrombinemia (-G 7248/7249 and ARG 340 TRP).

Hypoprothrombinemia is an uncommon hereditary coagulation defect characterized by low levels of biologically active prothrombin. Automated fluorescence-based DNA sequence analysis of amplified genomic DNA was used to define prothrombin gene regions from a patient with severe functional hypoprothrombinemia and little detectable prothrombin antigen. Two changes that alter amino acid sequence were observed: a deletion of one nucleotide (-G, 7248/7249) in exon 8 of one allele, causing a frameshift at codon 249/250 that results in premature termination of translation; and a C --> T change resulting in the substitution of tryptophan (TGG) for arginine (CGG) at amino acid 340 in exon 10 of the prothrombin gene. Computer modeling of the thrombin molecule confirmed that arginine 340 is located at the surface of the thrombin molecule, which points to the aqueous solvent. As tryptophan is a highly hydrophobic amino acid, the Arg --> Trp change may be associated with instability of the thrombin molecule.

Adult↗
PubMed1997

alpha-thalassemia caused by a 16 bp deletion in the 3' untranslated region of the alpha 2-globin gene including the first nucleotide of the poly A signal sequence.

We have identified a 16 bp deletion in the 3' untranslated region of the alpha 2-globin gene, including the first nucleotide of the polyadenylation signal sequence. The propositus, her mother and one of her brothers, all heterozygotes for the above deletion, have mild microcytic anemia. This is the first description of a deletion in the alpha gene involving both the 3' untranslated region and the polyadenylation signal sequence, causing alpha-thalassemia.

Anemia↗
PubMed1996

Clinical features and studies of erythropoiesis in Israeli Bedouins with congenital dyserythropoietic anemia type I.

Congenital dyserythropoietic anemia (CDA) type I is a rare macrocytic anemia of unknown etiology. In the present study, we redefined the clinical and laboratory picture of CDA type I, some of its pathogenic aspects, and the association with thalassemia-like features in 20 patients, all of whom belong to one Bedouin tribal group and are probably descended from a common ancestor. In each case ultrastructural studies of bone marrow (BM) erythroblasts showed the classic morphological findings of CDA type I. Serological tests for CDA type II were negative. The clinical picture was variable, but mostly benign. Some patients displayed elevated hemoglobin A2 levels or high ratio of alpha- to non-alpha- globin. However, neither family studies nor complete sequence analysis of the beta-globin was compatible with beta-thalassemia. Increased erythropoiesis was manifested by a high number of BM erythroid burst-forming units. Serum erythropoietin was also elevated. BM flow cytometry studies demonstrated arrest of erythroid precursors in the S phase of the cell cycle. The ultrastructural morphological features of the erythroid precursors, showing peripheral chromatin condensation, suggest apoptosis. Additional studies are indicated to define the molecular basis of this disease.

Adolescent↗
PubMed1996

Hodgkin disease in children: reduced tailored chemotherapy for stage I-II disease.

PURPOSE: Between January 1982 and January 1994, 46 children with stage I-II Hodgkin disease were treated with a tailored regimen to maintain a high cure rate while reducing toxicity. PATIENTS AND METHODS: Forty-six previously untreated children with stage I-II Hodgkin disease received four to six courses of cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), tailored according to clinical response. Staging was based on various imaging modalities and gallium scan, but surgical staging was not performed. Radiotherapy was given only to bulky mediastinal disease. RESULTS: The median age at diagnosis was 13 years (range 4-18) and only 4 of 46 children had B symptoms. The majority (31 of 46) had stage II disease; 10 had bulky mediastinal disease. Nodular sclerosis histology predominated (32 of 46). Gallium scan was positive in 66% of the patients who were evaluated. Forty-three patients (93%) achieved complete remission after planned therapy. Thirty-six patients (78%) received chemotherapy alone, and 10 (22%) received combined-modality treatment. Fifteen children (33%) completed treatment with only four courses of COPP/ABVD. Overall freedom from relapse was 87% and overall survival was 98% with a median follow-up of 5 1/2 years. Long-term treatment-related morbidity was found mainly in patients receiving radiotherapy. CONCLUSION: Comprehensive clinical staging combined with tailored COPP/ABVD therapy according to response results in excellent disease control and may reduce toxicity.

Adolescent↗
PubMed1996

Ala244Val is a common, probably ancient mutation causing factor VII deficiency in Moroccan and Iranian Jews.

We investigated the molecular basis for factor VII (FVII) deficiency in Israel and found that 13 patients were homozygous and 10 heterozygous for a C to T substitution at nucleotide 10648 of the FVII gene. This predicted an Ala244Val change and was associated with decreased FVII activity and antigen level. Of the 36 Ala244Val positive alleles, 20 were observed in patients of Moroccan origin, 10 in Iranian-Jewish patients and 6 in patients of other origins. A computer model of the serine protease domain of FVII suggested that the Ala244Val substitution may cause distortion of the entire protein structure. Intragenic polymorphic sites analyses disclosed a founder effect for the Moroccan and Iranian-Jewish patients. A survey of the Ala244Val mutation revealed an allele frequency of 1:42.5 in Moroccan Jews and 1:40 in Iranian Jews. As Moroccan Jews have been separated from Iranian Jews for more than two millennia, the data suggest that the Ala244Val mutation occurred in ancient times.

Alanine↗
PubMed1994

Systematic use of automated fluorescence-based sequence analysis of amplified genomic DNA for rapid detection of point mutations.

Several approaches are now available for screening populations for known mutations in a given gene. However, for detection of multiple mutations in a population that has not been characterized or for detection of new mutations, the value and efficiency of these screening procedures decreases. Although more than 100 different beta-thalassemia mutations have so far been described, the spectrum of mutations in the Eastern Mediterranean and Israel has not been defined in detail. We have used automated fluorescence-based DNA sequence analysis of PCR-amplified genomic DNA employing a cycle-sequencing strategy coupled with advanced analysis software to rapidly detect beta-thalassemia mutations in Israeli patients. This method enabled rapid identification of eight different mutations in 10 patients, including two rare mutations, one of which has never been described in this geographic region. Our results show that automated fluorescence-based DNA sequence analysis of amplified genomic DNA is a rapid and reliable method for detection of point mutations and small deletions or insertions in both heterozygous and homozygous states. This approach is particularly effective for a relatively small gene such as beta-globin, but it can also be used for rapid detection of mutations in large genes by first sequencing clusters of exons and intron/exon borders.

Automation↗
PubMed1994

Chronic childhood idiopathic thrombocytopenia purpura: long-term follow-up.

An understanding of the natural history of childhood chronic idiopathic thrombocytopenia purpura (ITP) could contribute to a rational therapeutic approach to its treatment, which remains controversial. In our retrospective study of 92 children with ITP, 22 had a chronic course and were followed for 3-14 years (median 8.6 years). Treatment, when indicated, was individualized: 4 patients (18.2%) did not receive any treatment, 14 (63.6%) received steroids only, while 4 (18.2%) were treated with steroids and one of the following: high-dose gamma globulin (4 patients), splenectomy (2 patients) or immunosuppressive therapy (2 patients). During follow-up, 14 patients (63.6%) achieved complete remission, 5 (22.7%) partial remission and only 3 (13.5%) remained severely thrombocytopenic, with minimal bleeding tendency. Eleven patients (50%) responded to the initial prednisone course (1-5 mg/kg/day), but showed a marked decrease in platelet count when steroids were tapered off. In view of the high rates of complete and partial remission and the mild course of the few non-responding patients, it is suggested that with adequate supportive therapy, follow-up problems and fatalities can be kept to a minimum. We believe that aggressive therapy, such as splenectomy, should be reserved for the rare symptomatic and severely thrombocytopenic patient.

Child↗
PubMed1994

Hb Taybe (alpha 38 or 39 THR deleted): an alpha-globin defect, silent in the heterozygous state and producing severe hemolytic anemia in the homozygous.

Several alpha-chain hemoglobin variants have been described as responsible, in homozygous or compound heterozygous patients, for a chronic hemolytic disease that overlaps thalassemia and Heinz bodies hemolytic anemia phenotypes. These variants are present in trace amounts together with some Hb H in the lysate of the patients. In the asymptomatic heterozygous carriers, they are usually not detected by electrophoretic methods. Hb Taybe is an example of such an unstable and thalassemic alpha-hemoglobin variant. This hemoglobin was observed in a young Israeli Arab woman having suffered since birth from a severe and highly regenerative hemolytic anemia for which she was splenectomized at age sixteen. The structural abnormality was characterized by protein chemistry as the deletion of a threonine residue at position alpha 38 or 39 and assigned to the alpha 1 gene by selective DNA sequencing. This structural modification is localized in helix C, which is a highly conserved 3(10) helix participating in the alpha 1 beta 2 contact and close to the alpha 1 beta 1 interface. The propositus and two siblings, who were also anemic, were found to be homozygous for the molecular defect, although the abnormal Hb was not detected in the latters. Consanguinity in this family demonstrated the threshold effect in the clinical manifestations of such alpha-gene disorders since heterozygotes were clinically and biologically normal.

Adult↗
PubMed1994

The pattern of bone disease in transfusion-dependent thalassemia major patients.

Twenty-eight patients with thalassemia major were treated with frequent blood transfusions for 10-25 years. Eleven (39%) had radiographic signs of osteoporosis, and four (14%) presented with fractures. Keeping hemoglobin level above 9.0 g/dl reduced osteoporosis and the incidence of fractures but did not prevent them. Osteonecrosis of the femoral head and distal femur, not previously reported, was noted in two patients.

Adolescent↗
PubMed1994

Ambulatory treatment with ceftriaxone in febrile neutropenic children.

We conducted a prospective nonrandomized study of outpatient therapy with ceftriaxone as a single agent in 50 episodes of fever and neutropenia in children treated with various myelosuppressive regimens for different malignancies. All patients underwent clinical and radiological evaluation and blood/urine cultures taken before starting therapy. Patients with dehydration, hypotension, rigor and clinical exit-site infection of indwelling right-sided catheters were excluded. Forty-one patients completed an antibiotic course of 7 days: in 12 patients fever returned to normal on day 2, in 10 patients on day 3, and in 8 patients on day 4. The duration of neutropenia following the initial febrile episode was 3-10 days. In some patients fever returned to normal after 2 days, but neutropenia persisted up to 10 days. Two patients were bacteremic--Escherichia coli in one, and Acinetobacter/Staphylococcus coagulase negative in another; all isolates were sensitive to ceftriaxone. In nine episodes, antimicrobial therapy was modified because of persistent fever > 39 degrees C in five patients, bacteremia in two, enterocolitis in one, breakthrough fever in two, and bronchopneumonia in one. The low incidence of bacterial isolation is probably attributed to the selection of patients with low risk features. Patients and parents complied with and favored outpatient therapy to hospitalization.

Ambulatory Care↗
PubMed1994

Long-term intravenous deferoxamine treatment for noncompliant transfusion-dependent beta-thalassemia patients.

With the introduction of long-term subcutaneous administration of deferoxamine (DFO), there has been a decline in the morbidity and mortality of transfusion-dependent beta-thalassemia patients. However, since the use of subcutaneous DFO is hindered by poor compliance, long-term i.v. DFO therapy has been attempted in order to improve compliance, prevent excessive iron accumulation and extend survival. Thirteen patients (aged 5.4-18.4 years) were started on i.v. home administration of DFO (100 mg/kg per day) via an exteriorized, tunneled right atrial catheter (Hickman type). After a median follow-up of 36 months, the mean ferritin levels had dropped significantly (5,117 +/- 1,737 to 1,816 +/- 1,062 micrograms/l. P = 0.0001). None of the patients developed new endocrine or cardiac diseases due to iron overload. Patients beginning therapy at an early age (< or = 11 years) showed a tendency for improved growth parameters at the end of the treatment period. Two patients developed moderately high frequency sensorineural hearing loss. One patient developed a right atrial thrombus. The line infection rate was low (1.7 episodes per 1,000 patients days). In view of the grave prognosis for iron overloaded patients and the fact that oral chelators are not yet readily available, we recommend this form of therapy for the young, noncompliant beta-thalassemia patient, despite the occasional complications observed.

Adolescent↗
PubMed1993

Hb Shelby [beta 131(H9)Gln-->Lys] in association with Hb S [beta 6(A3)Glu-->Val]: characterization, stability, and effects on Hb S polymerization.

When first tested for abnormal hemoglobins, a 2-year-old boy, appeared to have Hb F, Hb S and Hb A2. Confirmatory testing revealed a beta chain variant inherited from his father and beta S from his mother. Analysis of tryptic peptides in conjunction with automated DNA sequence analysis showed that the variant hemoglobin was Hb Shelby [beta 131(H9)Gln-->Lys (CAG-->AAG)]. Heat and mechanical stabilities of various liganded Hb Shelby tetramers were compared to those of Hb A and Hb S. Oxy-Hb Shelby precipitated more readily than oxy-Hb A, but was much more stable than oxy-Hb S during mechanical agitation. In contrast, oxy-Hb Shelby was much less stable than oxy-Hb A and oxy-Hb S following heat treatment. Met-Hb Shelby was most unstable compared to other liganded forms of Hb Shelby, while deoxy- and carbonmonoxy-forms of Hb Shelby showed similar heat-induced precipitation rates. These data indicate that heat instability of Hb Shelby is accompanied by heme oxidation, and that denaturation by mechanical agitation occurs in the absence of heme oxidation. Hb Shelby, like Hb A, can form hybrids with Hb S which participate in polymer formation in vitro. However, Hb S/Hb Shelby hybrids copolymerized with Hb S less than A/S hybrids. Since the patient's MCHC value is normal, this finding coupled with the elevated Hb A2 and Hb F levels, both of which are known to inhibit polymerization of Hb S, may contribute to the patient's mild clinical presentation.

Base Sequence↗
PubMed1993

Transient erythroblastopenia of childhood. Evidence for cell-mediated suppression of erythropoiesis.

PURPOSE: T cell-mediated red cell aplasia in a 4 1/2-year-old child with transient erythroblastopenia of childhood (TEC) is described. PATIENTS AND METHODS: Erythropoiesis was studied by assessing the colony growth of marrow erythroid progenitors at the time of diagnosis and during recovery. RESULTS: The colony-forming unit-erythroid (CFU-E) growth of whole marrow at diagnosis was only 28% that of the control. T-cell depletion of the patient's marrow was followed by a more than fivefold increase in CFU-E growth, as compared with 20% inhibition of CFU-E and 40% inhibition of burst-forming unit-erythroid (BFU-E) growth in control marrow. The number of colony-forming unit-granulocyte-macrophage (CFU-GM) in both control and patient's marrow was not significantly altered by all of these manipulations. During early and late recovery, CFU-E and BFU-E growth improved substantially, and the effect of T-cell depletion diminished. Increased numbers of peripheral T-suppressor lymphocytes, as well as activation of natural killer (NK) cells and high levels of interferon, all consistent with viral infection, were found at presentation. Clinical recovery was associated with normalization of T-suppressor lymphocyte number. CONCLUSIONS: The results suggest that in this child with TEC, a preceding viral infection may have caused activation of suppressor T-cells and interferon secretion leading to cell-mediated suppression of erythropoiesis.

Anemia↗
PubMed1992

T-cell acute lymphoblastic leukemia following therapy of rhabdomyosarcoma.

Multiple studies have documented an increased risk of secondary malignancies in patients receiving alkylating agents. Secondary leukemia following chemotherapy accounts for about 20% of all secondary neoplasms; most are acute nonlymphocytic. Secondary acute lymphoblastic leukemia has rarely been reported in either adult or childhood cancer. We report the development of acute T-cell lymphoblastic leukemia in a child following successful treatment of a paravertebral embryonal rhabdomyosarcoma (ERS). Southern blot analysis of DNA extracted from the T-cell lymphoblasts, using probes homologous to loci on the short arm of chromosome 11; P-calcitonin, P40.1 and H-ras, did not demonstrate the chromosomal loss of heterozygosity (LOH), a common feature of embryonal rhabdomyosarcoma. The data presented support the assumption that de novo leukemia emerged following treatment of the primary malignancy.

DNA, Neoplasm↗
PubMed1991

Hepatic iron overload: quantitative MR imaging.

Iron deposits demonstrate characteristically shortened T2 relaxation times. Several previously published studies reported poor correlation between the in vivo hepatic 1/T2 measurements made by means of midfield magnetic resonance (MR) units and the hepatic iron content of iron-overloaded patients. In this study, the authors assessed the use of in vivo 1/T2 measurements obtained by means of MR imaging at 0.5 T using short echo times (13.4 and 30 msec) and single-echo-sequences as well as computed tomographic (CT) attenuation as a measure of liver iron concentration in 10 severely iron-overloaded patients with beta-thalassemia major. The iron concentrations in surgical wedge biopsy samples of the liver, which varied between 3 and 9 mg/g of wet weight (normal, less than or equal to 0.5 mg/g), correlated well (r = .93, P less than or equal to .0001) with the preoperative in vivo hepatic 1/T2 measurements. The CT attenuation did not correlate with liver iron concentration. Quantitative MR imaging is a readily available noninvasive method for the assessment of hepatic iron concentration in iron-overloaded patients, reducing the need for needle biopsies of the liver.

Adolescent↗
PubMed1990

Infantile idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) in childhood is a benign disease, as only 10% to 20% of the patients have a chronic course. A retrospective study of 57 ITP patients ranging in age from four months to two years revealed that 30% of them proceeded to chronicity. Unlike ITP in the general pediatric population, chronic infantile ITP was characterized by male predominance, a high frequency of preceding viral infections, and lack of responsiveness to any of the known modalities of treatment.

Child↗