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Biomedical subjects

R Zaizov

Publications and source records attributed to R Zaizov.

At least 73 records · Page 4Linked to original sources
PubMed1994

A new deletional alpha-thalassemia detected in Yemenites with hemoglobin H disease.

A new large deletion from the human alpha-globin gene cluster is characterized. It involves at least 39 kb and includes the two alpha-globin genes, the theta 1-gene, all the pseudogenes, and the two hypervariable regions (HVRs), interzeta-HVR and alpha-globin 3'HVR. The conserved zeta-globin gene has been identified in various restriction fragments of abnormal size. The new deletion was found in four unrelated Israeli patients with Hb H disease, all originating in Yemen, and has been designated--YEM. It is the only two-gene deletion identified in this ethnic group.

Autoradiography↗
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

Bone scintigraphy in nonsurgically treated Ewing's sarcoma at diagnosis and follow-up: prognostic information of the primary tumor site.

In order to detect skeletal metastases in patients with Ewing's sarcoma, bone scanning is commonly used. However, little information is available about the scintigraphic aspects of the primary Ewing's sarcoma during non-surgical treatment and follow-up. We studied retrospectively the significance of bone scintigraphic findings at the primary tumor site of 58 patients with a Ewing's sarcoma. These patients had chemotherapy and radiotherapy. At presentation 53/58 patients showed an increased tracer uptake at the primary tumor site while 5 patients with a pelvic or sacral bone localization had a normal scan. Bone scans made during treatment and more than 2 years thereafter in the 32 eligible patients demonstrated three patterns. In 16 patients the hot spot disappeared and no local tumor recurrence was encountered. In the other 16 patients the high uptake at the primary tumor site either persisted or diminished first to a normal uptake after a median period of 18 months (range 12-36 months) and returned again to a high uptake within 6-12 months. In these patients local Ewing's sarcoma was still present in 13, while in the other 3 cases a benign disorder (fracture, ectopic bone formation) was the underlying cause. These findings suggest that in non-surgically treated Ewing's sarcoma persisting increased tracer uptake or its recurrence is highly suspicious for the presence of Ewing's sarcoma, while bone scans becoming negative and remaining so for more than 12 months suggest the absence of local tumor.

Bone Neoplasms↗
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

Childhood B-cell non-Hodgkin's lymphoma in Israel.

The non-Hodgkin's lymphomas of childhood and adolescence are a heterogeneous group of diseases that constitute 7-10 percent of all pediatric malignancies. Major strides have been made in recent years in understanding the pathogenesis of lymphomas at a molecular level but have not yet led to a modification of clinical management. Between 1973 and 1992, 112 children with B-cell non-Hodgkin's lymphoma were diagnosed. The median age was 5.7 years, with male to female ratio of 3 to 1. Fifty percent presented with abdominal masses, mostly confined to the ileo-ceccal region and to the retroperitoneum. In 39 percent there was head and neck involvement, with 15 percent jaw lesions. Until 1978 patients were treated with the Beilinson Medical Center (BMC) protocol, which yielded only 26 percent disease-free survival for stage IV patients. The introduction of the LMB-86 regimen significantly improved the disease-free survival of patients with advanced stage III and IV disease (84 and 68 percent, respectively). Bone marrow (over 70 percent blasts) and central nervous system involvement remain the major prognostic criteria.

Adolescent↗
PubMed1994

Genetic alterations involving chromosome 1p in children with neuroblastoma.

Neuroblastoma is a common childhood tumor of the sympathetic nervous system, characterized by N-myc amplification and loss of heterozygosity (LOH) for sequences on chromosomes 1p, 11q and 14q. Using restriction fragment length polymorphism analysis, the constitutional and tumor genotypes were compared for LOH on 1p in 25 children with neuroblastoma at diagnosis: 19 in stages III-IV, 5 in stages I-II and one in IVs. The genetic alterations observed on chromosome 1p were frequent in the early and advanced stages. Thirty-three percent of the alterations were found in patients under the age of 1 year, and in one patient with IVs. It is concluded that 1p alterations were identified in children with neuroblastoma in early stages and infants and thus of no prognostic relevance. 1p genetic alterations may be early events in neuroblastoma.

Blotting, Southern↗
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

Peripheral blood stem cells as a source for hemopoietic recovery following autologous bone marrow transplantation in childhood malignancy.

In an attempt to improve hemopoietic recovery after autologous bone marrow transplantation (ABMT), a project of peripheral blood stem cells (PBSC) harvest was initiated. Thirty-six children awaiting ABMT underwent 126 PBSC harvests primed by a conventional scheduled chemotherapy course and rGMCSF 5 micrograms/kg per day/s.c. Ages ranged from 12 months to 19 years and weight from 9 to 84 kg. PBSC harvest was carried out using the Fenwall CS 3000 Plus with the small volume collection chamber at a maximum whole blood flow rate of 15-45 ml/min; total volume processed was 1,700-10,000 ml. Total nucleated cells per collection was 0.35-5.62 x 10(8) cells per kg, and the number of CD34+ cells, 0.23-1.1 x 10(6)/kg. The number of colony forming units-granulocyte macrophages (CFU-GM) varied in these heavily pretreated patients from 0 to 5.3 CFU-GM x 10(4)/kg per collection. Immunophenotyping of the cells collected was performed by double staining for CD34, CD33, CD15, CD71, Ia and CD56. Most of the CD34+ cells were found to be CD38+; some were CD33+ and some CD33-. Low coexpression of CD34+ CD71+ cells may correlate with the low proliferating capacity of PBSC as compared to the BM cells. To date 22 children have undergone transplantation using combined autologous PBSC and bone marrow. We conclude that PBSC harvest is a feasible and safe procedure even in small children, and can be successfully performed following scheduled chemotherapy and administration of growth factors, resulting in substantial yield, also in heavily pretreated patients. This procedure is recommended in responding high risk patients at the stage of minimal residual disease and may replace ABMT in the future.

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↗
PubMed1994

Aminohydroxy propylidene bisphosphonate (APD) treatment improves the clinical skeletal manifestations of Gaucher's disease.

OBJECTIVE: To evaluate the long-term effects and safety of aminohydroxy propylidene bisphosphonate (APD) treatment on the frequency and severity of the clinical skeletal manifestations of Gaucher's disease. METHODOLOGY: Five adolescents who suffered from recurrent bone crisis episodes and atraumatic bone fractures due to Gaucher's disease were treated with APD for 14 to 83 months. RESULTS: During the 6 years before treatment, the patients suffered from 6 to 17 bone crisis episodes, or 1 to 2.8 episodes per patient per year. Three patients were free from bone crisis episodes during 14 to 32 months of ADP treatment, while two patients had two such episodes during 60 and 83 months of APD treatment (these represent a decrease in bone crisis episodes from 1 and 2.8 per year to 0.4 and 0.3 per year, respectively). Although four patients suffered from 1 to 3 atraumatic bone fractures during the 6 years preceding treatment (a total of 10 fractures), only one patient sustained a fracture on APD treatment (total of 219 months of treatment). Using APD was not associated with clinical side effects, biochemical aberrations, significant changes in liver and kidney function, or changes in serum levels of the hormones regulating mineral metabolism. In all patients, a band-like metaphyseal sclerosis appeared on radiography of the long bone. However, APD did not interfere with bone growth. CONCLUSIONS: The marked clinical improvement in the clinical skeletal manifestations of Gaucher's disease and the absence of toxic side effects in adolescent patients treated with APD support previous findings in three adult patients on the efficacy of APD and indicate possibilities for its use in inducing prolonged remissions in affected patients.

Adolescent↗
PubMed1993

Distortion in the parental transmission of HLA-A2 haplotypes (locus A,B).

The parental transmission of HLA-2 antigen in association with the epitopes BW4 and BW6 (class I HLA haplotypes locus A,B) was analyzed in sons and daughters from 42 families in which one of the parents carried the HLA-A2 antigen. When the parental transmission of A2 BW4 and A2 BW6 was compared, it was observed that a significantly higher number of siblings inherited the haplotype A2 BW4 from the paternal than from the maternal haplotype. Although the number of cases is small, the mode of inheritance of haplotype A2 BW6 was completely different. The genetic distortion in the transmission of HLA-2 BW4 and HLA-2 BW6 was observed in children of both sexes.

Cytotoxicity, Immunologic↗
PubMed1993

Mode of inheritance of HLA haplotypes locus A,B in siblings of different sexes.

METHOD: Forty-eight parents and 172 children were typed for class I HLA antigens, locus A,B. RESULTS: Although the number of cases is small, we observed: (1) a significantly decreased number of sons born after a first delivery of a son, as compared to a first delivery of a daughter; (2) significantly increased sharing of maternal class I HLA antigens between the firstborn son and his brothers from higher birth orders, as compared to his sisters; and (3) HLA-A2 antigen, which is known to be involved in HLA restricted cytotoxic reactions in the recognition of minor histocompatibility antigens, was inherited in subsequent deliveries of sons as compared to daughters in a significantly higher frequency from the paternal than from maternal HLA haplotype. The results suggest that sharing of identical maternal HLA haplotypes between brothers may aid to decrease the degree of maternal sensitization to fetal antigens, and lack of HLA-2 antigen in maternal cells from sons as compared to daughters may avoid maternal HLA-A2 restricted cytotoxic reactions toward the male fetus.

Adult↗
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↗
PubMed1993

Improved results in osteogenic sarcoma 1973-79 vs. 1980-86: analysis of results from a single center.

Analysis of treatment results in osteogenic sarcoma patients with classical limb primary tumors and without metastasis at diagnosis or major protocol violations showed improved prognosis with a minimum follow-up of over 5.5 years when divided by years of treatment for all event-free survivors. Twelve patients treated in 1980-86 had a 5-year disease-free survival of 67% and 9 treated in 1973-79 had a 5-year disease-free survival of 33% (P = 0.0368). The improvement appeared to reflect the increase in the intensity of the chemotherapy utilized. Definitive surgery, amputation or limb salvage did not affect the outcome. With these surgical approaches the disease-free survival was 67% and 60% respectively.

Adolescent↗
PubMed1992

[Evans syndrome in a child].

A Bedouin girl, aged 2 3/12, was first seen at the age of 9 months for sequential onset of Coombs-positive hemolytic anemia and immune thrombocytopenia. Comprehensive laboratory workup revealed no underlying disease. Evans' syndrome, relatively rare in childhood, was diagnosed and corticosteroid therapy initiated. She responded well and normal hemoglobin and thrombocyte counts were achieved within a month. All attempts at tapering-off the dose of corticosteroids resulted in relapses, until high-dose intravenous gamma-globulin was given.

Adrenal Cortex Hormones↗