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N J Weinreb

Publications and source records attributed to N J Weinreb.

12 recordsLinked to original sources
PubMed2002

Skeletal aspects of Gaucher disease: a review.

In Gaucher disease, a genetic deficiency in the activity of the lysosomal enzyme beta-glucocerebrosidase (acid beta-glucosidase) causes monocytes and macrophages to store excessive amounts of glucocerebroside in lysosomes. The resulting distended cells are called Gaucher cells, and the pathology associated with this condition stems from the accumulation of Gaucher cells in organ systems. The skeletal manifestations are probably the most disabling aspect of the disease. Patients commonly experience bone pain, some suffer bone crises, and up to 20% have impaired mobility. Radiological findings include Erlenmeyer flask deformity, osteopenia, osteosclerosis, osteonecrosis, fractures and bone marrow infiltration. Findings from the Gaucher Registry show that nearly all patients with Gaucher disease have radiological evidence of skeletal involvement, and the majority have a history of serious skeletal complications. Skeletal involvement follows three basic processes: focal disease (irreversible lesions such as osteonecrosis and osteosclerosis), local disease (reversible abnormalities adjacent to heavily involved marrow such as cortical thinning and long bone deformity) and generalized osteopenia. Infarctions are involved in some of the skeletal manifestations, but the mechanisms causing high rates of bone turnover and failure of remodelling are not known. The availability of a beta-glucocerebrosidase-deficient mouse model of Gaucher disease with long-term survival should help elucidate the skeletal pathology in Gaucher disease and may ultimately lead to improved management of skeletal complications.

Animals↗
PubMed2002

Response of Gaucher bone disease to enzyme replacement therapy.

In Gaucher disease, enzyme replacement therapy usually reduces liver and spleen volumes and improves haematological abnormalities within 1 year. In contrast, skeletal manifestations of Gaucher disease are thought to respond more slowly. For example, decreased bone marrow glycolipid infiltration and increased bone mineral density have been reported to take up to 3-4 years of treatment. In this report, we present recent studies using T1- and T2-weighted MRI and quantitative chemical shift imaging that demonstrate decreases in abnormal glucocerebroside infiltration and increases in normal fat content of bone marrow within the first year of treatment. There was no obvious relationship between age, gender, splenectomy status or genotype and the response of bone marrow to therapy. Although the dose of enzyme replacement therapy may be related to bone marrow response, no significant relationship was demonstrated in this report. Long-term enzyme replacement therapy induces continued degradation of Gaucher cell deposits, reconversion of fat marrow and increased bone mineral density. This treatment is also associated with improved or non-progressive bone symptoms and functional status in most adult patients, and it prevents the new occurrence of bone pain and bone crisis in nearly all patients. The development of more sensitive, quantitative imaging methods will help to evaluate disease severity better and to assess the response to therapy.

Adolescent↗
PubMed2000

The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease.

BACKGROUND: The Gaucher Registry, the largest database of patients with Gaucher disease (GD) worldwide, was initiated to better delineate the progressive nature of the disorder and determine optimal therapy. This report describes the demographic and clinical characteristics of 1698 patients with GD before they received enzyme replacement therapy. METHODS: Physicians worldwide who treat patients with GD were invited to submit prospective and retrospective data for an ongoing registry, using standardized data collection forms, for central processing and review. RESULTS: Most patients were from the United States (45%) and Israel (17%), but patients are from 38 countries. Most (94%) had type 1 GD, fewer than 1% had type 2, and 5% had type 3. Mutant allele frequency data, available for 45% of patients, showed the most common alleles to be N370S (53%), L444P (18%), 84GG (7%), and IVS2+1 (2%). Twenty-five percent of L444P homozygotes (13 of 52 patients) had type 1 GD phenotype. Mean age at diagnosis in patients with the N370S/N370S genotype was 27.2 years (SD, 19.7 years); in L444P/L444P patients, 2. 3 years (SD, 3.2 years). Histories of bone pain and radiological bone disease were reported by 63% and 94% of patients, respectively; both were more likely in asplenic patients than in patients with spleens. Mean spleen and liver volumes were 19.8 and 2.0 multiples of normal, respectively. Anemia and thrombocytopenia were present in 64% and 56%, respectively. Thrombocytopenia was present in 13% of asplenic patients. CONCLUSIONS: The Gaucher Registry permits a comprehensive understanding of the clinical spectrum of GD because of the uniquely large sample size. The Registry will be useful in evaluating the effects of specific therapies in GD and the possible influences of environment, ethnicity, and genotype on the natural history of the disorder.

Adolescent↗
PubMed1998

Gaucher disease: recommendations on diagnosis, evaluation, and monitoring.

BACKGROUND: Timely diagnosis and continued monitoring of patients with type I Gaucher disease is critical because skeletal involvement can permanently disable patients and visceral organ involvement can lead to abdominal pain and secondary hematologic and biochemical complications. OBJECTIVE: To seek clinical consensus for minimum recommendations for effective diagnosis and monitoring of patients with type I Gaucher disease. PARTICIPANTS, EVIDENCE, AND CONSENSUS PROCESS: Contributing authors collaborated in quarterly meetings over a 2-year period to synthesize recommendations from peer-reviewed publications and their own medical experiences. These physicians care for most patients with Gaucher disease in the United States and serve as the US Regional Coordinators for the International Collaborative Gaucher Group Registry, the world's largest database for this disorder. CONCLUSIONS: The definitive method of diagnosis is enzyme assay of beta-glucocerebrosidase activity. Schedules differ for monitoring complications of type I Gaucher disease, depending on symptoms and whether enzyme replacement therapy is used. Hematologic and biochemical involvement should be assessed by complete blood cell count, including platelets, acid phosphatase, and liver enzymes, at baseline and every 12 months in untreated patients and every 3 months and at enzyme replacement therapy changes in treated patients. Visceral involvement should be assessed at diagnosis using magnetic resonance imaging or computed tomographic scans. Skeletal involvement should be assessed at diagnosis using T1- and T2-weighted magnetic resonance imaging of the entire femora and plain radiography of the femora, spine, and symptomatic sites. Follow-up skeletal and visceral assessments are recommended every 12 to 24 months in untreated patients, and every 12 months and at enzyme replacement therapy changes in treated patients.

Bone and Bones↗
PubMed1998

Euthanasia and doctor-assisted suicide: responses by oncologists and non-oncologists.

PURPOSE: Public interest concerning euthanasia and doctor-assisted suicide is creating ethical dilemmas in the health care profession. We surveyed the views of oncologists and non-oncologists in Florida. METHODS: Physicians responded to an attitudinal questionnaire. The data collected were compared with standard statistical methods. RESULTS: Both oncologists and non-oncologists had similar opposition to euthanasia on philosophic or general grounds, with more opposition on general grounds expressed by oncologists. Both groups preferred better pain control and improved quality of life rather than euthanasia, but more oncologists than non-oncologists favored this alternative. Both groups admitted to participation in passive euthanasia, with little support for active euthanasia and doctor-assisted suicide. However, should the acts of euthanasia and doctor-assisted suicide become legalized, more non-oncologists than oncologists would agree to participate. CONCLUSION: In Florida, more opposition to aspects of the termination of life was expressed by oncologists than by non-oncologists.

Adult↗
PubMed1996

Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase.

OBJECTIVES: The incidence and severity of growth retardation in children with type 1 Gaucher disease and the response to enzyme replacement therapy with alglucerase were studied. STUDY DESIGN: A retrospective analysis of growth in 99 children and adolescents with type 1 Gaucher disease before treatment, and in 54 of those subjects during treatment, was done. Growth was compared with gender, age, and dosage of replacement enzyme. RESULTS: Linear growth was normal in the first 1 to 2 years of life and then decelerated. Height was at or below the 5th percentile in 50% of all subjects immediately before treatment. The mean z score was -1.49 (95% confidence interval, -1.83 to -1.16), corresponding to the 6.8th percentile for height. Seventy-two percent were below the 50th percentile and 50% were at or below the 5th percentile for mid-parental height (p <0.001). One and one-half years after treatment was started, the estimated mean z score for all subjects was -1.01, which corresponds to the 16th percentile for height. Normal growth was achieved within 4 to 30 months in eight of nine subjects who were at or below the 5th percentile. It occurred only in those receiving higher doses (60 to 120 U/kg per 4-week period) of alglucerase. There was a significant association between z scores for height before treatment and liver enlargement (r= 0.57; p < 0.01). CONCLUSIONS: Half of the subjects who manifest type 1 Gaucher disease in childhood have growth retardation. Treatment with adequate amounts of modified enzyme replacement was effective in normalizing linear growth.

Adolescent↗
PubMed1975

Spurious polycythemia.

Spurious polycythemia is not a primary disease process. It sometimes may be nothing more than an unusual, but normal, physiologic state. In other instances, however, it is associated with a true abnormality of plasma volume. Although there is probably overlap between these extremes, differentiation of these subclasses may be of prognostic significance. The elevation in hematocrit bears no relation to morbidity, and, because there is no evidence of abnormal erythroid proliferation, reduction of red cell volume via phlebotomy or myelosuppression is inappropriate. Nonhematologic parameters, particularly hypertension, are the major factors of significance in the substantial cardiovascular morbidity in spurious polycythemia, and they demand attentive and aggressive management.

Blood Volume↗
PubMedDate not supplied

Debility, unspecified: a terminal diagnosis.

OBJECTIVE: To determine whether the diagnosis "debility, unspecified" (ICD-9 code 799.3) is appropriate for use with terminally ill patients and to define the criteria for assigning the diagnosis. DESIGN: A survey of patient charts to determine the clinical characteristics of a defined cohort. SETTING: A comprehensive hospice program with average daily census over 500 patients. PATIENTS: All patients who died in the hospice program during the period from January through October, 1993 and were assigned a diagnosis of "debility, unspecified" (ICD-9, 799.3). MEASUREMENTS: For each patient, the following information was recorded: demographics, level of function (ability to carry out activities of daily living), presence of major system disease, other illnesses, any other appropriate ICD-9 coded diagnosis. RESULTS: The diagnosis of "debility, unspecified" was confirmed in 50 out of 53 cases. All 50 patients exhibited multiple comorbid conditions. Major organ system impairment included central nervous system (96 percent of patients), cardiopulmonary (76 percent of patients), skin integrity (42 percent of patients), and sepsis at the time of admission (30 percent of patients). The average survival for these patients was 67 days and the median survival was 20 days. In none of the 50 patients was there a single major system impairment of a degree to warrant a specific terminal diagnosis. CONCLUSIONS: The use of the ICD-9 code 799.3 "debility, unspecified" as a terminal diagnosis was confirmed to be appropriate based on survival and hospice length of stay data and on the fact that no patients exhibited a singular major system disease sufficient to support a terminal prognosis. A decision tree for assigning the diagnosis is presented.

Activities of Daily Living↗