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Biomedical subjects

A Abrahamov

Publications and source records attributed to A Abrahamov.

At least 19 recordsLinked to original sources
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

Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo.

Red blood cell (RBC) membranes from patients with the thalassemic and sickle hemoglobinopathies carry abnormal deposits of iron presumed to mediate a variety of oxidative-induced membrane dysfunctions. We hypothesized that the oral iron chelator deferiprone (L1), which has an enhanced capacity to permeate cell membranes, might be useful in chelating these pathologic iron deposits from intact RBCs. We tested this hypothesis in vitro by incubating L1 with RBCs from 15 patients with thalassemia intermedia and 6 patients with sickle cell anemia. We found that removal of RBC membrane free iron by L1 increased both as a function of time of incubation and L1 concentration. Thus, increasing the time of incubation of thalassemic RBCs with 0.5 mmol/L L1 from 0.5 to 6 hours, enhanced removal of their membrane free iron from 18% +/- 9% to 96% +/- 4%. Dose-response studies showed that incubating thalassemic RBC for 2 hours with L1 concentrations ranging from 0.125 to 0.5 mmol/L resulted in removal of membrane free iron from 28% +/- 15% to 68% +/- 11%. Parallel studies with sickle RBCs showed a similar pattern in time and dose responses. Deferoxamine (DFO), on the other hand, was ineffective in chelating membrane free iron from either thalassemic or sickle RBCs regardless of dose (maximum, 0.333 mmol/L) or time of incubation (maximum, 24 hours). In vivo efficacy of L1 was shown in six thalassemic patients whose RBC membrane free iron decreased by 50% +/- 29% following a 2-week course of L1 at a daily dose of 25 mg/kg. As the dose of L1 was increased to 50 mg/kg/d (n = 5), and then to 75 mg/kg/d (n = 4), 67% +/- 14% and 79% +/- 11%, respectively, of their RBC membrane free iron was removed. L1 therapy--both in vitro and in vivo--also significantly attenuated the malondialdehyde response of thalassemic RBC membranes to in vitro stimulation with peroxide. Remarkably, the heme content of RBC membranes from L1-treated thalassemic patients decreased by 28% +/- 10% during the 3-month study period. These results indicate that L1 can remove pathologic deposits of chelatable iron from thalassemic and sickle RBC membranes, a therapeutic potential not shared by DFO. Furthermore, membrane defects possibly mediated by catalytic iron, such as lipid peroxidation and hemichrome formation, may also be alleviated, at least in part, by L1.

Anemia, Sickle Cell↗
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

Gynecologic and obstetric aspects of Gaucher's disease: a survey of 53 patients.

OBJECTIVE: We report our experience on the gynecologic and obstetric features of 53 female patients with Gaucher's disease. STUDY DESIGN: Each patient was interviewed for a detailed medical history, and all underwent a complete physical examination and laboratory work-up. RESULTS: Delay of puberty onset was encountered in two thirds of the patients without subsequent infertility. Heavy menstrual bleeding was a major problem and was best treated with low-dose oral contraceptives. Of the 102 spontaneous pregnancies' 25 (24.5%) ended in spontaneous first-trimesters abortions; 72 continued beyond the twenty-second week. Nine patients (27.7%) were diagnosed as having Gaucher's disease during their first pregnancies. Aggravation of thrombocytopenia and anemia were prominent features, but antepartum blood transfusion was not required. Early postpartum hemorrhage and fever were increased after both cesarean and vaginal deliveries. Development of bone crisis in seven women during the third trimester and early postpartum periods recurred in subsequent pregnancies. Genotypes had not influenced the gynecologic or obstetric manifestations. CONCLUSIONS: Gynecologic and obstetric complications play a significant role in this patient population, representing an additional burden to female patients with Gaucher's disease.

Abortion, Spontaneous↗
PubMed1995

An efficient new cannabinoid antiemetic in pediatric oncology.

Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administered (18 mg/m2 in edible oil, p.o.) to eight children, aged 3-13 years with various hematologic cancers, treated with different antineoplastic drugs for up to 8 months. The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each antineoplastic treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible.

Adolescent↗
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↗
PubMed1994

HCG contamination of alglucerase: clinical implications in low-dose regimen.

Alglucerase (Ceredase) is currently the treatment of choice for patients with symptomatic Gaucher disease. The contamination of this placental enzyme with human chorionic gonadotropin (hCG) has raised concern regarding possible endocrinological complications. We examined 32 patients treated with low-dose alglucerase and 27 untreated patients as controls, and found no significant clinical differences between the two groups: no prepubertal children were affected, no menstrual irregularities were reported, and all hCG levels were well within normal range. Conversely, our finding of a statistically significant difference between the groups underscores the importance of initiating parallel studies of hCG contamination in patients receiving high-dose protocol.

Adult↗
PubMed1993

Low-dose high-frequency enzyme replacement therapy for very young children with severe Gaucher disease.

Six children with a mean age of 4.6 years (range 2.5-7), suffering from severe Gaucher disease, were treated with low-dose high-frequency intravenous enzyme replacement (Ceredase, Genzyme, U.S.A.) for a period of 10-24 months. Although, in general, these patients were more severely affected than previously reported patients, the results of the treatment were as satisfactory as those obtained by using much higher doses at low frequency. In addition to regression of organomegaly and improvement of haematological abnormalities, we observed two unique clinical responses in three patients: two showed decreased tendency to bacterial infections, associated with improvement in neutrophil chemotaxis, and one patient, with type 3 Gaucher disease, showed some improvement in neurological findings. Several measures were taken to ameliorate the burden of the high-frequency treatment. These included implantation of venous access devices, establishment of a home-treatment programme and the application of effective local anaesthesia. Therefore the low-dose high-frequency protocol appears to be both an effective and feasible alternative to the costly high-dose low-frequency protocols even in very young children.

Child↗
PubMed1990

Absence of natural killer cells in a child with pure red blood cell aplasia.

A 16-year old boy was known to suffer from red blood cell (RBC) aplasia from the age of 4 years. Peripheral blood lymphocytes (PBL) from the patient were found to lack natural killer (NK) cytotoxic activity, even after stimulation with alpha-interferon. His PBL also lacked Leu-7+ and Leu-11+ cells, although his granulocytes showed normal expression of the Leu-11 marker. The lack of NK cells did not seem to result from the various immunosuppressive treatments he received, since the NK deficiency was noted 2 years after he stopped receiving such treatment. The possibility is discussed that lack of NK cells may lead to the development of RBS aplasia if NK cells play a role in promoting the production of RBC.

Antigens, Surface↗
PubMed1989

Natural course of atrial septal aneurysm in children and the potential for spontaneous closure of associated septal defect.

Atrial septum aneurysm (ASA), usually involving the region of the fossa ovalis, has rarely been described in children. In this study, the incidence and natural course of this anomaly were prospectively evaluated in 3,500 children referred for echocardiographic examination. ASA was found in 35 patients, 19 female and 16 male (1.0%). Patients were 6 years of age or younger at the time of diagnosis and 18 were neonates. None of the 750 children with normal echocardiograms had ASA. The most common associated lesion was atrial septal defect (ASD), which occurred in 24 of the 35 patients (69%). Other associated cardiac lesions were ventricular septal defect in 10, pulmonary stenosis in 5, patient ductus arteriosus in 4 and coarctation or interruption of the aorta with subaortic membrane in 2. No clinical complications were associated with ASA. Six patients with complex heart disease died. When associated with ASD, the direction of the ASA motion and that of the shunt found by Doppler echocardiography were similar. Fourteen patients with ASD were followed for 0.5 to 4 years. In 8 the ASD closed and in 6 the ASA disappeared. In 6 patients the ASD and ASA persisted until the end of the follow-up (p less than 0.01). Thus, the incidence of ASA in children in this series was higher than previously presumed and usually was associated with other cardiac anomalies, mainly ASD. In children, ASA tends to disappear with age and may have a role in spontaneous closure of associated ASD.

Abnormalities, Multiple↗
PubMed1987

Impaired kinetic properties of hypoxanthine-guanine phosphoribosyl transferase as a cause of uric acid nephropathy in early infancy.

A 6-month-old infant presented with failure to thrive, hyperuricaemia and renal insufficiency. The hyperuricaemia was due to uric acid over-production. The level of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity was found to be normal. However, a two-fold increase in the Km of the enzyme to hypoxanthine as well as in the Vmax values was observed. It seems therefore, that in cases of uric acid over-production, screening tests of HGPRT activity may be insufficient and additional kinetic properties of the enzyme should be tested.

Acute Kidney Injury↗