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Biomedical subjects

A Zimran

Publications and source records attributed to A Zimran.

At least 55 records · Page 3Linked to original sources
PubMed1998

Echocardiographic assessment of pulmonary hypertension in Gaucher's disease.

BACKGROUND: Enzyme therapy has been shown to decrease the signs and symptoms of Gaucher's disease. A few patients, however, develop pulmonary hypertension on such treatment. We investigated the frequency of pulmonary hypertension in Gaucher's disease. METHODS: We studied 134 adults with type 1 Gaucher's disease, including 73 patients on enzyme replacement, with echocardiography. We measured tricuspid incompetence (TI) with continuous-wave doppler. Pulmonary hypertension was indicated by a TI gradient of more than 30 mm Hg. FINDINGS: Nine (7%) patients had pulmonary hypertension: all were treated and six had undergone splenectomy. Chest radiographs confirmed the presence of pulmonary hypertension in these patients as well as in most patients with TI gradients of 25-29 mm Hg. INTERPRETATION: The confounding effects of disease severity and splenectomy in many treated patients precluded definitive conclusion of cause and effect. Nonetheless, we found an unexpectedly high rate of pulmonary hypertension and recommended routine echocardiographic monitoring of all treated and untreated patients with type 1 Gaucher's disease. We also suggest consideration of treatment withdrawal if the TI gradient progresses to more than 30 mm Hg.

Adult↗
PubMed1998

Geographic variance in the frequency of the t(14;18) translocation in follicular lymphoma: an Israeli series compared to the world.

It has been suggested that differences in the frequency of the t(14;18) translocation in follicular lymphoma might explain ethno-geographic variation in the incidence of these tumors. We tested Israeli follicular lymphoma patients for the frequency of the t(14;18) translocation, and reviewed the published literature, comparing the frequency in our series with data from different parts of the world. Tissue specimens from 36 Israeli follicular lymphoma patients were tested for presence of the translocation by PCR amplification of the MBR breakpoint. Twenty-two of the 36 patients (61%) tested positive. A systematic search of the literature yielded 35 papers reporting the frequency of the t(14;18) translocation in follicular lymphoma. We analyzed cytogenetic data and molecular data separately. For each method, data were pooled from all studies within each of three geographical regions - USA, East Asia and Europe. Pooled data from cytogenetic studies show a low frequency of the translocation in the Far East (38%) compared to the USA (71%), with an intermediate frequency found in Europe (61%). Molecular studies show a similar frequency of the translocation in the Far East and Europe, significantly lower than the frequency in pooled data from American studies. The frequency in our Israeli series is relatively high, comparable to that detected in the USA. We suggest that the apparent geographical differences we describe are unlikely to be caused by a difference in the biology of the tumor, and are more likely due to technical and methodological factors. We conclude that it is unlikely that differences in the frequency of the t(14;18) translocation explain the difference in the epidemiology of lymphoma between East and West.

Adult↗
PubMed1998

The nature and extent of jaw involvement in Gaucher disease: observations in a series of 28 patients.

A wide variety of osteoarticular pathoses plague the clinical course of many patients with Gaucher disease. Osseous lesions involving the jaws have been described, usually as isolated case reports. The purpose of this study was to ascertain the nature and extent of mandibulo-maxillofacial pathosis in 28 patients with documented Gaucher disease by means of panoramic radiography. Twenty-five of the 28 patients displayed radiographic evidence of jaw involvement. The most prevalent finding was gross widening of marrow spaces; frank radiolucencies, endosteal scalloping, cortical thinning, root resorption, and inferior displacement of the mandibular canal or effacement of its cortices were also seen. A previously unreported finding was delayed eruption of permanent teeth, which was seen in more than one half of the patients who were under 20 years of age. Osseous changes throughout the jaws may be more common than previously suspected and may alert the dentist to the presence of the disease.

Adolescent↗
PubMed1998

Asymptomatic Gaucher disease implications for large-scale screening.

Gaucher disease, the most prevalent genetic disorder among Ashkenazi Jews, is characterized by significant phenotypic heterogeneity. Because seven mutations account for more than 96% of the disease alleles in this population, large-scale screening is feasible, and genotyping is commercially available. To date, only 400 Gaucher patients have been diagnosed in Israel, although 2,500 patients are predicted by gene frequency; hence, there is the probability that those uncovered by population screening will prove to be very mild or asymptomatic since these patients have generally escaped medical attention until now. We studied objective and subjective aspects in 68 asymptomatic/very mild patients, followed for a mean of 2.6 years, to assess the implications of identifying many more such patients if large-scale screening were to be implemented. We found there were no medically significant changes in disease severity during follow-up. The patients' subjective reports of their general health status were similar to those of normal subjects, and there were no significant changes in quality of life during follow-up. Our findings suggest that asymptomatic/mild Gaucher patients do not require frequent monitoring; there is no justification for "prophylactic" enzyme therapy in this group, and, hence, no rationale for large-scale screening in the Ashkenazi population. Furthermore, one needs to be concerned with the adverse effects of labeling large numbers of asymptomatic individuals as affected because of the potential for stigmatization and discrimination.

Adolescent↗
PubMed1998

Low-dose low-frequency imiglucerase as a starting regimen of enzyme replacement therapy for patients with type I Gaucher disease.

The issue of the interplay of optimal dosage and frequency regimens for enzyme replacement therapy in type I Gaucher disease has been a source of controversy during the 7 years since the introduction of the placenta-derived enzymatic preparation in 1991. We present the results of treatment with the human recombinant form of the enzyme in 28 type I Gaucher patients, who have been treated for 6 to 24 months. As long as cost is an important factor in the management of patients with Gaucher disease, low-dose low-frequency imiglucerase promises satisfactory clinical improvement without compromising quality of life.

Adolescent↗
PubMed1998

Ethical considerations for enzyme replacement therapy in neuronopathic Gaucher disease.

Enzyme replacement therapy for Gaucher diseases, the most prevalent lysosmal storage disease, was originally approved by the FDA for type I patients and has proven to be both safe and effective in reducing hepatosplenomegaly and improving the hematological parameters. However, the use of enzyme treatment in both neuronopathic forms has heretofore been on an investigational or trial basis, with reports of progression of neurological deterioration even at very high doses. To date, there are no guidelines for clinicians with regard to enzyme replacement therapy in the neuronopathic forms of metabolic diseases. Herein. we discuss strategies derived from the literature vis-à-vis treatment of very premature babies and from the Jewish Halachic point of view. In conclusion. we describe recommendations for the ethical treatment and/or withdrawal of treatment, as well as practical guidelines for dosage regimens, in children with neuronopathic Gaucher disease.

Ethics, Medical↗
PubMed1997

Abdominal ultrasound findings mimicking hematological malignancies in a study of 218 Gaucher patients.

Gaucher disease, the most prevalent sphingolipidosis, generally presents with splenomegaly, anemia, and thrombocytopenia. Hence, hematologists are often the specialists involved in diagnosis and management of these patients. We present ultrasonographic characteristics in a cohort of 218 consecutive Gaucher patients evaluated in our clinic during the past 5 years. Our data emphasize the high prevalence of lesions mimicking hematological malignancies in Gaucher disease. One fifth of 184 non-splenectomized patients had intra-splenic lesions, 6% of all patients had similar lesions in the liver, and 32% of 34 splenectomized patients (but none of the other patients) had marked retroperitoneal or peri-portal lymphadenopathy. The presence of splenic lesions correlated with age and splenic size, but not with extent of bone involvement or genotype. Interestingly, they were not affected by reduction in splenomegaly following enzyme replacement therapy. The importance of these findings is to include Gaucher disease in the differential diagnosis of splenic or hepatic lesions, especially in Ashkenazi Jews. Conversely, they are relevant for follow-up of all Gaucher patients, including asymptomatic individuals, because of the reported increased incidence of hematological malignancies in Gaucher disease.

Adolescent↗
PubMed1997

Cytokine mRNA in Gaucher disease.

Gaucher disease, the most common glycolipid storage disease, is caused by glucocerebrosidase deficiency, resulting in accumulation of glucocerebrosides within the macrophages of the reticuloendothelial system. The disease is characterized by great phenotypic heterogeneity, which can be explained only in part by the various mutations in the glucocerebrosidase gene, and by the amount of storage material in affected organs and tissues. Therefore, it has been postulated that some of the biochemical and clinical features may be related to the fact that "Gaucher" cells, as activated macrophages, express and release cytokines such as IL-1beta, IL-8, IL-6 and TNF-alpha which play a role in different physiological processes. In the present study, cytokine mRNA expression was measured in monocytes isolated from Gaucher patients and from healthy controls, using RT-PCR methodology with semiquantitative analysis. We found significantly increased expression of IL-1beta mRNA, as well as a trend to elevated TNF-alpha mRNA in Gaucher patients relative to healthy individuals. There were no statistically significant differences between Gaucher disease patients and controls with respect to two other tested cytokines (IL-6 and IL-8).

Adult↗
PubMed1997

Distinct haplotype in non-Ashkenazi Gaucher patients with N370S mutation.

A new polymorphism, in intron 7 of glucocerebrosidase gene, has been identified in Gaucher Disease patients. It seems to appear only in Pv1.1- alleles bearing the N370S mutation. This new sub-haplotype was only identified in Portuguese patients, of origins spanning all of the Portuguese continental territory. This finding indicates that, in the Portuguese, mutation N370S has existed in the context of two slightly different haplotypes and thus must be relatively ancient.

Gaucher Disease↗
PubMed1997

Use of enzyme replacement therapy for Gaucher disease during pregnancy.

OBJECTIVE: To date there has been little published experience with enzyme replacement therapy in pregnant women with symptomatic type I Gaucher disease. STUDY DESIGN: We describe six patients, including three with repeated early pregnancy loss, five of whom successfully carried pregnancies to term; the last pregnancy was terminated because of pulmonary hypertension. RESULTS: All pregnancies were uneventful and five resulted in healthy newborns. CONCLUSION: We concluded that in patients with Gaucher disease of childbearing age,for whom obstetric complications are an important symptom of the disease, pregnancy is not contraindicated (unless there is evidence or suspicion of pulmonary hypertension) and treatment should not be interrupted because the clinical improvement engendered by enzyme replacement therapy is conducive to fewer complications during pregnancy and delivery and post partum.

Abortion, Habitual↗
PubMed1997

Gaucher's disease: genetic counselling and population screening.

Genetic counselling for Gaucher's disease requires a comprehensive approach, including accurate diagnosis at both the enzymatic and molecular levels, and assessment of disease severity. These goals are particularly challenging given the great allelic and phenotypic heterogeneity encountered in this disorder. Counselling should address the specific concerns of the counsellee, which may be related to evaluation of an affected person, or to reproductive options in couples at risk. Advances in both diagnosis and treatment have led to increased ascertainment of cases and carriers through population based screening, rather than through affected probands, raising new ethical and medical dilemmas. This chapter outlines practical issues in counselling for the various forms of Gaucher's disease, based on current data and experience.

Gaucher Disease↗
PubMed1997

Accuracy of ultrasonography in assessing spleen and liver size in patients with Gaucher disease: comparison to computed tomographic measurements.

A comparison was made between volume measurements of spleen and liver by ultrasonography and by computed tomography, the two most common modes of assessment of organ size in patients with Gaucher disease, who require frequent follow-up measurements. The two measurements showed a high degree of correlation within a broad range for both spleen and liver volumes. An algorithm for conversion of one measurement to the other was derived for both spleen and liver.

Adolescent↗