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Ari Zimran

Publications and source records attributed to Ari Zimran.

At least 37 records · Page 2Linked to original sources
PubMed2004

Rheological determinants in patients with Gaucher disease and internal inflammation.

The purpose of this study was to determine whether the inflammatory response in patients with Gaucher disease (GD) is accompanied by enhanced adhesiveness/aggregation of both red and white blood cells. Sixty patients with GD and matched controls were included. The degree of erythrocyte and leukocyte adhesiveness/aggregation was determined by using a simple slide test and image analysis. Patients with GD had significantly elevated concentrations of fibrinogen (328 vs. 262 mg/dl, P < 0.0001) and accelerated erythrocyte sedimentation rates (27 vs. 13 mm/H, P < 0.005). This was accompanied by a significantly enhanced degree of erythrocyte (75 vs. 85, P < 0.0001) and leukocyte (3.5 vs. 1.3, P < 0.002) adhesiveness/aggregation. The low-grade, smoldering, and subclinical internal inflammation in individuals with GD is accompanied by an increased degree of erythrocyte and leukocyte adhesiveness/aggregation. These findings might have rheological consequences in terms of microcirculatory slow flow and tissue hypoxemia.

Adult↗
PubMed2004

Bone density changes with enzyme therapy for Gaucher disease.

Gaucher disease is the most common lysosomal storage disease. Enzyme replacement therapy engenders improvement in hematological and visceral parameters; however, improvement in bone density (BMD) with treatment has not been confirmed. This study presents follow-up of BMD in the first ten patients in Israel treated with low-dose recombinant enzyme for up to 108 months. BMD at femoral neck and lumbar spine was determined by dual-energy X-ray absorptiometry (DEXA) at the start of the trial, after 3-6 months, after 18-24 months, and at the most recent follow-up. BMD in all patients was very low at onset and never normalized. There was a decrease in BMD in all patients at 3-6 months. Older patients (four women, two men; >30 years of age) showed some improvement in BMD during treatment. Younger patients (four females; 18-23 years of age) did not show a statistically significant improvement. These findings might reflect the failure of patients with Gaucher disease to achieve expected peak bone density at appropriate chronological milestones despite treatment. Nonetheless, the z-scores of the older patients were better than those of the younger patients, implying some catch-up period. Yet, some patients with Gaucher disease evince rapid onset of osteoporosis in early adulthood. Enzyme treatment per se, as well as attendant improved well-being and increased physical activity, may induce amelioration in BMD at this later stage. One may consider adding anti-osteoporosis therapy in young adults to induce earlier "catch up" to peak bone mass, and then enzyme replacement in later adulthood to prevent decrements in bone mass related to Gaucher cell infiltration.

Adolescent↗
PubMed2004

Pregnancies in Gaucher disease: a 5-year study.

OBJECTIVE: The study was undertaken to investigate the outcome of pregnancies in Gaucher disease, particularly in enzyme-treated women. STUDY DESIGN: A retrospective study was performed of pregnant women evaluated at a referral clinic. RESULTS: There were 43 (17 treated, 26 untreated) women with 66 pregnancies (23 treated, 43 untreated). The live birth rate was 78.3% among treated, 86.0% among untreated. One treated woman had three spontaneous abortions; 3 untreated women had one each. Four pregnancies in each group had postpartum bleeding, 7 requiring transfusions. Postpartum infections were prevalent among treated. Cesarean sections were generally for historic reasons. There was no exacerbation of Gaucher disease, except one bone crisis. CONCLUSION: Most untreated women with milder disease enjoyed an uncomplicated course. Enzyme-treated patients (ie, with more severe disease) had more bleeding and infections post partum, but few had spontaneous abortions. Hematologic consultation is recommended. A review of world experience with pregnant patients with Gaucher disease is included.

Adult↗
PubMed2004

N-brain natriuretic peptide: correlation with tricuspid insufficiency in Gaucher disease.

NT-pro-brain natriuretic peptide (NT-proBNP) values are correlated with right ventricle dysfunction in pulmonary hypertension and have been recommended as a prognostic marker for symptomatic primary pulmonary hypertension. The purpose of this pilot study was to determine whether NT-proBNP values correlate with mild to moderate pulmonary hypertension in Gaucher disease. The NT-proBNP assay was performed on sera from patients with type I (non-neuronopathic) Gaucher disease who were known to have tricuspid insufficiency (TI) gradient values on echocardiography that were normal (TI<20 mmHg), borderline (TI=25-29 mmHg), or abnormal (TI>or= 30 mmHg) over time. There was a statistically significant correlation (p=0.05) between mean NT-proBNP values and TI gradient group: mean NT-proBNP for normal TI gradient (n=20 patients)=133.3 (range: 46-445)pg/ml; mean NT-proBNP for borderline TI gradient (n=17 patients)=288.7 (range: 81-1088)pg/ml; and mean NT-proBNP for elevated TI gradient (n=10 patients)=1034.2 (73-6703)pg/ml. Treatment status was not correlated with TI gradient or NT-proBNP values. Thus, in this pilot study of Gaucher disease that included patients with mild to moderate pulmonary hypertension, NT-proBNP was correlated with echocardiographic findings. Further studies will be required to ascertain if NT-proBNP can be used for diagnosis and monitoring of these patients.

Adolescent↗
PubMed2004

Gaucher disease type 1: revised recommendations on evaluations and monitoring for adult patients.

For patients with type 1 Gaucher disease, challenges to patient care posed by clinical heterogeneity, variable progression rates, and potential permanent disability that can result from untreated or suboptimally treated hematologic, skeletal, and visceral organ involvement dictate a need for comprehensive, serial monitoring. An updated consensus on minimum recommendations for effective monitoring of all adult patients with type 1 Gaucher disease has been developed by the International Collaborative Gaucher Group (ICGG) Registry coordinators. These recommendations provide a schedule for comprehensive and reproducible evaluation and monitoring of all clinically relevant aspects of this disease. The initial assessment should include confirmation of deficiency of beta-glucocerebrosidase, genotyping, and a complete family medical history. Other assessments to be performed initially and at regular intervals include a complete physical examination, patient-reported quality of life using the SF-36 survey, and assessment of hematologic (hemoglobin and platelet count), visceral, and skeletal involvement, and biomarkers. Specific radiologic imaging techniques are recommended for evaluating visceral and skeletal pathology. All patients should undergo comprehensive regular assessment, the frequency of which depends on treatment status and whether therapeutic goals have been achieved. Additionally, reassessment should be performed whenever enzyme therapy dose is altered, or in case of significant clinical complication.

Adult↗
PubMed2004

Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy.

Gaucher disease, the most prevalent lysosomal storage disorder, is characterized by hepatosplenomegaly, hypersplenism, and rarely, neurological involvement. The most variable symptoms relate to skeletal disease, and both onset and progression are difficult to predict on the basis of genotype. This review describes findings from a large referral clinic (> 500 patients) and from the literature in the decade since the advent of specific enzyme replacement therapy. Such therapy is effective in reducing visceral and hematological involvement, but its greatest advantage as regards the skeleton is prevention of irreversible damage. Avascular necrosis of the joints-particularly the hips but also the knees and shoulders-and pathological fractures of the long bones including the ribs, as well as episodic "crises' of bone pain in children and young adults, are common manifestations. Various imaging modalities should be performed at baseline for life-long monitoring, and then as required because of specific complaints. Surgical interventions such as joint arthroplasties are important adjuvant treatments in this population; presurgical hematological profiling plus antibiotic cover and postoperative pain control are equally critical. Opportunities for orthopedic consultations with senior surgeons are not abused by our patients. These reflect disease-related morbidity, with greater numbers of requests being made by patients requiring enzyme therapy, who by definition have more severe disease characteristics.

Adolescent↗
PubMed2004

Increased prevalence of cholelithiasis in Gaucher disease: association with splenectomy but not with gilbert syndrome.

GOALS: The purpose of this study is to ascertain the incidence of gallstones among adult patients with type 1 Gaucher disease and whether the presence of the UDPGT1 polymorphism (Gilbert syndrome), increases the incidence of gallstones. BACKGROUND: Cholelithiasis was been observed among patients with type I Gaucher disease with variable frequency. Too, studies have addressed the possibility of an association between Gilbert syndrome and formation of bilirubinate gallstones in hereditary spherocytosis wherein, like Gaucher disease, there is hemolysis of blood cell membranes. METHODS: Medical records of all adult patients with type 1 disease in a referral clinic were reviewed for evidence of gallstones or cholecystectomy. Blood samples were collected for molecular analysis for Gilbert syndrome. RESULTS: Of 323 adult patients, 82 patients (25.4%), 54 women (65.9%) and 28 men (34.1%), had evidence of gallbladder disease (P < 0.001 relative to normal white controls). There was a statistically significant increase (P < 0.001) for all groups above the ages of 20 years other than for men aged 40 to 49 years. There was a statistically significant association between splenectomy and both cholelithiasis (P = 0.022) and Gilbert syndrome (P = 0.002). CONCLUSIONS: This study highlights an increase incidence of cholelithiasis but not Gilbert syndrome among patients with Gaucher disease. Storage of glycolipid per se or an immune reaction to storage, may explain these findings.

Adult↗
PubMed2003

Dental profile of patients with Gaucher disease.

BACKGROUND: This study was conducted to determine whether patients with Gaucher disease had significant dental pathology because of abnormal bone structure, pancytopenia, and coagulation abnormalities. METHODS: Each patient received a complete oral and periodontal examination in addition to a routine hematological evaluation. RESULTS: Gaucher patients had significantly fewer carious lesions than otherwise healthy carriers. Despite prevalence of anemia, there was no increase in gingival disease; despite the high incidence of thrombocytopenia, gingival bleeding was not noted; and despite radiological evidence of bone involvement, there was no greater incidence loss of teeth or clinical tooth mobility. CONCLUSIONS: These data represent the first survey of the oral health of a large cohort of patients with Gaucher disease. It is a pilot study of a unique population and the results of the investigation are indications for further research. Based on our findings, we recommend regular oral examinations with appropriate dental treatment for patients with Gaucher disease as for other individuals. Consultation between the dentist and physician, preferably one with experience with Gaucher disease, should be considered when surgical procedures are planned.

Journal Article↗
PubMed2003

Gaucher disease and the clinical experience with substrate reduction therapy.

Gaucher disease is caused by an enzymatic defect with consequent accumulation of glucocerebroside. Type I, the non-neuronopathic form, is rather common and panethnic. Patients may present with hepatosplenomegaly, anaemia, thrombocytopenia and skeletal or lung involvement. Enzyme replacement therapy ameliorates disease symptoms and signs; however, it involves lifelong intravenous therapy, is costly and is incapable of crossing the blood-brain barrier. Substrate reduction with N-butyldeoxynojirimycin (OGT 918) is a harbinger of oral iminosugars for glycolipid storage disorders. Long-term data in the seminal trial (100 mg three times per day), demonstrate safety and efficacy in adult type I patients naive to enzyme therapy, and suggest its application in patients unwilling or unable to receive enzyme replacement and tolerating side effects, including diarrhoea, weight loss, tremor and peripheral neuropathy (mostly reversible with dose reduction or withdrawal). Dose dependency was demonstrated with 50 mg three times per day. In patients stabilized on enzyme therapy switched from or in combination with enzyme, no deterioration in disease parameters was seen but side effects were as above. Although efficacy is less dramatic than enzyme treatment, it may be that plateaux are achieved asymptotically so therapeutic outcomes with OGT 918 may ultimately be comparable. Yet, given the above side effects and the lack of long-term experience, patients with very mild manifestations would probably not be appropriate candidates.

1-Deoxynojirimycin↗
PubMed2003

D-dimer assay in Gaucher disease: correlation with severity of bone and lung involvement.

The D-dimer assay as a marker of cross-linked fibrin may also be an indicator of active microvascular thrombosis, even in patients without overt hypercoagulation. In type I Gaucher disease, there is tremendous phenotypic variability that cannot be ascribed solely to different genotypes. Thus, there are no predictive tests to ascertain patients at risk for bone involvement, such as avascular necrosis, or lung disease, particularly pulmonary hypertension, which are two of the major causes of morbidity in Gaucher disease and which are slow to respond to enzyme replacement therapy. Previous studies to correlate these parameters with thrombophilic profiles have not been conclusive. Levels of D-dimers were assayed and compared to the presence of avascular necrosis and abnormally elevated TI gradient among other variables, in 118 unselected adult patients (52 males) with Gaucher disease. Of these, 19 patients had very mild Gaucher disease (Severity Score Index, SSI < 5) and 23 had severe disease (SSI > 15); 29 had avascular necrosis; 37 were splenectomized (due to massive splenomegaly and hypersplenism). As an indirect measure of pulmonary hypertension, TI gradient was used: 90 patients had normal TI gradients (<25 mmHg), and 12 patients had abnormal TI gradients (>30 mmHg). There were significant correlations between D-dimers and avascular necrosis, splenectomy, and elevated TI gradient. Thus, the D-dimer assay may be potentially predictive of bone and lung involvement in Gaucher disease.

Female↗
PubMed2003

Platelet counts and interleukin-6 (IL-6) promoter polymorphism in patients with Gaucher disease.

INTRODUCTION: The purpose of this study was to ascertain whether polymorphism of the IL-6 promoter gene affects platelet counts among patients with Gaucher disease since it has been shown that in healthy individuals, the CC genotype is correlated with lower platelet counts. METHODS: Blood samples from all adult patients seen at a referral clinic during a 12 month period were taken for PCR analysis for the IL-6 promoter polymorphism. Platelet counts were culled from the records on date of presentation and prior to advent of enzyme replacement therapy where relevant. RESULTS: Of 138 Ashkenazi Jewish patients, 31 patients had platelet counts <60,000/mm 3 and 37 patients had normal platelet counts (>150,000/mm 3 ). Of the former group, 4/31 (13%) and of the latter group, 3/37 (8%), had the CC genotype. Although all seven patients had relatively mild Gaucher disease (only one required therapy), there was no statistically significant difference in allele frequency of the IL-6 promoter polymorphism in either group relative to healthy Ashkenazi Jews. CONCLUSION: Whether comparing patients with Gaucher disease with normal platelet counts or with thrombocytopenia to healthy Ashkenazi Jews, there was no difference in frequency of the CC state. Thus, the IL-6 promoter polymorphism may not influence Gaucher disease to induce lower platelet counts as shown in other normal Caucasians.

Adolescent↗
PubMed2003

Amyloidosis and gastric bleeding in a patient with Gaucher disease.

GOALS: To describe the clinical course of a patient with Gaucher disease who subsequently developed amyloidosis. BACKGROUND: We present a case of a splenectomized patient with Gaucher disease who developed portal hypertension secondary to an enlarged, cirrhotic-like liver, and recurrent life-threatening upper gastrointestinal bleeding. STUDY: Despite repeated diagnostic biopsies, amyloidosis was only ascertained after death. RESULTS: Albeit very rare, there are four other similar cases in the literature, but unlike these previous reports of concurrence of Gaucher disease and amyloidosis, in this patient the gastrointestinal symptoms were life-threatening but there was no evidence of gammopathy or renal disease. Also, this is the first patient who was treated with enzyme replacement therapy for 5 years prior to manifestation of amyloidosis. CONCLUSIONS: Coexistence of apparently unrelated diseases with Gaucher disease demands a greater awareness of abnormalities at the biochemical and/or molecular level to adequately manage patients with Gaucher disease, regardless of concurrent enzyme replacement therapy.

Adult↗
PubMed2002

Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry.

PURPOSE: Gaucher disease is the first lysosomal storage disorder to be treated with macrophage-targeted enzyme replacement therapy. Previous studies in relatively small numbers of patients demonstrated short-term efficacy of this treatment. This study describes the effects of 2 to 5 years of treatment on specific manifestations of type 1 Gaucher disease. SUBJECTS AND METHODS: Physicians reported data from 1028 patients to the Gaucher Registry. Assessment of response included serial measurements of hemoglobin concentration, platelet count, liver and spleen volumes, and the occurrence of bone pain and bone crises. RESULTS: Among anemic patients, hemoglobin concentration increased to normal or near normal within 6 to 12 months, with a sustained response through 5 years. In thrombocytopenic patients with intact spleens, the most rapid response occurred during the first 2 years, with slower improvement thereafter. The likelihood of achieving a normal platelet count decreased with increasing severity of baseline thrombocytopenia. In patients who had undergone splenectomy, platelet counts returned to normal within 6 to 12 months. Hepatomegaly decreased by 30% to 40% during follow-up; splenomegaly decreased 50% to 60%, but rarely to volumes below five times normal size. In patients with pretreatment bone pain or bone crises, 52% (67/128) were pain free after 2 years and 94% (48/51) reported no additional crises. CONCLUSION: Enzyme replacement therapy prevents progressive manifestations of Gaucher disease, and ameliorates Gaucher disease-associated anemia, thrombocytopenia, organomegaly, bone pain, and bone crises.

Adolescent↗
PubMed2002

C7 complement deficiency in an Israeli Arab village.

Deficiencies of terminal complement components, particularly the latter ones, are often detected because of increased susceptibility to Neisserial infections. Herein we document the first report of C7 deficiency among a highly inbred Arab population living in the lower Galilee region of Israel. Both biochemical and molecular analysis were performed on samples from infected survivors and parents of children who succumbed to Neisserial infections in a 4-year period. Only the index case who suffered recurrent infections and a sibling who had not suffered an infection during the outbreak were found to be C7-deficient. The mutation was found to be the one previously described to be prevalent among Israeli Jews of Moroccan ancestry (mutation G1135C). The implications of this finding are discussed in the context of family pedigree, the protective effect of complement deficiency, and the clinical outcome.

Adolescent↗
PubMed2002

Repeat abdominal ultrasound evaluation of 100 patients with type I Gaucher disease treated with enzyme replacement therapy for up to 7 years.

With the advent of enzyme replacement therapy for Gaucher disease, there was a need to assess response to treatment repeatedly over relatively short periods of time; hence abdominal ultrasound was used in our referral clinic because it was convenient, safe and inexpensive. In 100 treated patients monitored for 2-7 years, nearly all had reduction in hepatosplenomegaly. The per cent reduction was more dramatic in patients who started treatment when older than 16 years. This effect may be explained by a correlation between per cent reduction and degree of baseline organomegaly. Because children often initiate therapy sufficiently early to preclude developing massive organomegaly, the observed per cent reduction is commensurately less. For all patients treated for more than five years, plateau-ing in response was seen after the first three years of treatment. This study permits us to reconsider less frequent evaluations of organ volumes. Our findings also underscore the efficacy of enzyme replacement, but raise the question of the need for dose reduction as nearly normal organ volumes are achieved.

Abdomen↗