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Biomedical subjects

D Elstein

Publications and source records attributed to D Elstein.

At least 37 records · Page 2Linked to original sources
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

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

Skeletal involvement in Gaucher's disease.

Perhaps the most variable of all the symptoms attributed to Gaucher's disease is that of bone involvement, both in the Type 1 and Type 3 forms of the disease. Expression of skeletal involvement in Gaucher patients ranges from asymptomatic disease, with or without radiological signs, to symptomatic disease, which can be severe and engender considerable pain and disability. Herein we discuss the imaging techniques currently available to document the presence and progression of bone involvement as well as the various forms of medical and surgical management that are employed to help the Gaucher patient cope with skeletal disease.

Bone and Bones↗
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↗
PubMed1996

Effect of low-dose enzyme replacement therapy on bones in Gaucher disease patients with severe skeletal involvement.

Gaucher disease, the most common glycolipid storage disorder, is characterized by hepatosplenomegaly and skeletal involvement. Enzyme replacement therapy in both the high- and low-dose regimens has been shown to be effective in reducing the organomegaly and improving the hematological parameters of symptomatic patients with type I disease. Herein we report subjective and objective responses of bone-related complications after 2 to 4 years of low-dose enzyme replacement therapy in 14 adult type I patients with severe skeletal involvement pre-treatment. We discuss our results relative to those reported in patients on the high-dose regimen, as well as with reference to a single patient who developed new avascular necrosis despite objective improvement in radiological studies.

Adolescent↗
PubMed1996

Occurrence of Parkinson's syndrome in type I Gaucher disease.

Gaucher disease, the most prevalent glycolipid storage disorder, is classically subdivided into types according to the presence or absence of neurological involvement. Type I has hitherto been considered non-neuronopathic. We present six cases and a review of the literature of Parkinsonian symptoms in type I Gaucher disease patients. The hallmark of this atypical Parkinsonian syndrome is a relatively severe clinical course with early appearance of neurological signs in the 4th to 6th decade of life, aggressive progression of the signs and refractoriness to conventional anti-Parkinson therapy. We discuss the implications of these findings in the light of enzyme replacement therapy for Gaucher disease.

Adolescent↗
PubMed1996

Pulmonary function abnormalities in type I Gaucher disease.

The purpose of this study was to determine the prevalence of pulmonary function and radiographic abnormalities among patients with type I Gaucher's disease, and to analyse the relationship between the pulmonary involvement and genotype and clinical severity score. All patients attending the Gaucher clinic at the Shaare Zedek Medical Center, Jerusalem, Israel, during the years 1992-1993 were prospectively evaluated. Each patient had pulmonary function tests, chest radiography, clinical assessment in terms of degree of organ involvement, and genotype analysis. Of the 95 patients included in the study (mean +/- SD age 29 +/- 15 yrs), 68% had some pulmonary function abnormalities, most commonly a reduced FRC and transfer coefficient for carbon monoxide (Kco), found in 45% and in 42% of the patients respectively. Total lung capacity (TLC) was reduced in 22% of the patients and forced expiratory flows in approximately one third of the patients. Signs of airtrapping (elevated residual volume (RV) or RV/TLC) were seen in 18% of the patients. Males had a higher incidence of reduced expiratory flow than females, (forced expiratory volume in one second (FEV1) was reduced in 36% of males vs 5% of females). Chest radiographic abnormalities were found in 17% of the patients, although only 4% had severe changes. Patients with abnormal pulmonary function had a significantly higher severity score index than those with normal pulmonary function tests. There was no association between abnormal pulmonary function and genotype or age. In conclusion, abnormal pulmonary function is common among type I Gaucher patients. Pulmonary function tests show airways obstruction, with reduced expiratory flows, reduction in lung volumes and alveolar-capillary diffusion abnormality. The rate of progression and the clinical significance need to be determined.

Adolescent↗
PubMed1995

Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype.

Gaucher's disease is the most prevalent sphingolipid storage disease, characterised by substantial genetic and phenotypic variability. Cardiac manifestations are rare. We report 12 Arab Gaucher's disease patients, 2-20 years of age, who presented with oculomotor apraxia but only slight classic signs of the disease. All but the youngest had calcifications of the aortic or mitral valves or both. All these patients were homozygous for the rare point mutation D409H (1342C). Valvular calcifications increased with age and showed progression during 2 years of follow-up. Two of the oldest patients underwent aortic valve replacement, and one sibling had died suddenly at age 16, before this study, Corneal opacities were another common feature. The potentially fatal course of this Gaucher's disease variant, and the availability of a reliable PCR-based method for heterozygote detection, mean that population screening and genetic counselling in the geographic area at risk are important. Affected individuals should be closely monitored by echocardiography to gauge the need for valve replacement. The potential of enzyme replacement to prevent these cardiac complications cannot be ascertained at present, because of the high cost of therapy.

Adolescent↗
PubMed1995

[Frequency of the Gaucher mutation among recent Russian immigrants].

Gaucher's disease is frequent in the Ashkenazi Jewish population of Israel, with a gene frequency by molecular analysis of approximately 0.032, corresponding to a birth rate of 1:850. The recent immigration from the former Soviet Union brought more than 400,000 Jews, mostly of Ashkenazi descent. However, only a few cases of Gaucher's disease have been diagnosed. Possible explanations are lack of awareness of the signs of Gaucher's disease among Russian health workers and family practitioners in Israel, and a significantly lesser frequency of the Gaucher gene among Russian immigrants than among other Ashkenazi Jews in Israel and the US. We studied the frequency of the 1226G (N370S) mutation in a cohort of 202 recent immigrants from the former Soviet Union. We found 10 carriers (4.95%), indicating a decreased frequency of the Gaucher gene, but by extension, the probability of unidentified cases in need of treatment. Family practitioners should be aware of the possibility that heretofore misdiagnosed symptoms may be those of Gaucher's disease.

Emigration and Immigration↗
PubMed1995

Replacement therapy with imiglucerase for type 1 Gaucher's disease.

Gaucher's disease, the most common sphingolipidosis, is caused by deficiency of the lysosomal enzyme glucocerebrosidase. Therapy with alglucerase (the placental enzyme) is safe and effective at various dosing regimens. We report the use of low-dose imiglucerase (the recombinant enzyme) at two dosing schedules: 15 u/kg once fortnightly or 2.5 u/kg thrice weekly. Mean reductions in spleen and liver volumes achieved (in all ten patients) by imiglucerase at 12 months were 36.4% and 14.5%, respectively; mean increase in haemoglobin and platelet counts were 13.4% and 25.7%. There were no serious side-effects. No significant differences were observed between the two schedules. Low-dose low-frequency imiglucerase may be an alternative cost-effective approach with satisfactory clinical response and uncompromised quality of life.

Adolescent↗
PubMed1995

Prenatal molecular diagnosis of Gaucher disease.

Prenatal diagnosis of Gaucher disease, the most prevalent glycolipid storage disease, is based on a reliable enzyme assay of cells from amniocentesis or chorionic villous samples. However, this method cannot differentiate among the various forms of the disease. This report details four cases of prenatal diagnosis of Gaucher disease, three of which predate the use of molecular diagnosis. DNA mutation analysis to determine the genotype was predictive of the phenotypic status of the fetus and conformed to the genotype of an affected proband where available.

Adult↗
PubMed1995

Outcome of partial splenectomy for type I Gaucher disease.

Partial splenectomy was introduced to achieve the benefits of splenectomy and to avoid the risk of overwhelming infection in patients with symptomatic Gaucher disease. We observed regrowth of the splenic remnant, reemergence of preoperative symptoms, and new bone involvement among most of our patients who had undergone partial splenectomy. Enzyme replacement therapy has markedly limited indications for splenectomy, partial or total, for Gaucher disease.

Adolescent↗