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Biomedical subjects

A Achiron

Publications and source records attributed to A Achiron.

At least 19 recordsLinked to original sources
PubMed2001

APOE genotype is a major predictor of long-term progression of disability in MS.

BACKGROUND AND OBJECTIVE: The authors recently reported that the APOE epsilon4 allele is associated with significantly greater progression of disability in a 2-year follow-up of patients with MS. In this study, these findings are substantiated and extended in a much larger group of patients followed for up to 40 years. METHODS: Two hundred five patients with clinically definite MS who were genotyped for the APOE epsilon4 carrier state were included. Groups of patients with (n = 41) and without (n = 164) APOE epsilon4 alleles were compared for latency to expanded disability status scale (EDSS) scores of 4.0 and 6.0 by Kaplan-Meier analysis with the log rank test. The results were adjusted for age at onset and sex by Cox regression analysis. RESULTS: The APOE epsilon4 allele frequency in patients with MS (0.10) was similar to that in the general Israeli population. There was a significant effect of APOE genotype on the latency to reach EDSS 4.0 and 6.0 (p = 0.0002 and p = 0.0006 by two-tailed log rank test). Median latencies were shorter by 12 and 11 years in the APOE epsilon4 group for these outcomes. These results were significant after adjustment for age at onset and sex. CONCLUSIONS: The APOE epsilon4 allele is associated with significantly faster progression of disability in MS. This is the first genetic factor to be identified with a major impact on the progression of disability in this disease.

Adult↗
PubMed2001

3-D surface reconstruction of multiple sclerosis lesions using spherical harmonics.

A new approach to approximate the 3-D shape of multiple sclerosis (MS) lesions and to calculate their volumes is presented. The suggested method utilizes sets of MS lesion contours taken from segmented MR images and approximates their 3-D surfaces by spherical harmonics. This method was applied to obtain 3-D reconstructions of in vivo and simulated MS lesions and to calculate their volumes. The results show good geometrical approximations of the original MS lesions' 3-D shapes and good consistency in volume estimation independent of the size of the lesions. The average volume estimation error was smaller than the commonly used technique of slice stacking (15.5 +/- 13.4% and 13.1 +/- 10.1% vs. 25.0 +/- 17.0%). The method presented here offers a tool for analyzing the geometrical characteristics of MS lesions in 3-D as well as their volumes. The geometrical information may potentially serve as an additional clinical index for monitoring the disease.

Algorithms↗
PubMed2001

Development of the human fetal corpus callosum: a high-resolution, cross-sectional sonographic study.

OBJECTIVE: To establish reference ranges during human pregnancy for normal fetal corpus callosum dimensions. DESIGN: In a prospective, cross-sectional study of 258 fetuses between 16 and 37 weeks of gestation, measurements of the length, width, and thickness at the level of the anterior mid-body of the corpus callosum were performed, using high-resolution, transvaginal and transabdominal transducers. RESULTS: The mean length of the corpus callosum was 27.2 (standard deviation, 1.2; 95% confidence interval, 26.02-28.37) mm. Width and thickness of the corpus callosum were 5.6 (standard deviation, 1.6; 95% confidence interval, 5.41-5.82) mm and 1.9 (standard deviation, 0.7; 95% confidence interval, 1.87-2.06) mm, respectively. The size of the corpus callosum as a function of gestational age was expressed by regression equations: length (mm) = -20.40 + 1.92 x gestational age; width (mm) = -0.052 + 0.225 x gestational age; thickness (mm) = -0.174 + 0.085 x gestational age. The dimension-gestational age correlation coefficients were: r = 0.779 for length, r = 0.676 for width and r = 0.494 for thickness; these were statistically significant (P < 0.01). The maximum increase in thickness and width of the corpus callosum occurred between 19 and 21 weeks' gestation, while its length followed a constant growth rate. The normal mean length, width and thickness of the corpus callosum per week, and the 95% confidence limits, were defined. CONCLUSIONS: The present study offers normative measurements of the fetal corpus callosum and may facilitate a more objective diagnosis of its congenital abnormalities.

Corpus Callosum↗
PubMed2001

Late-onset multiple sclerosis.

OBJECTIVE: The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. DESIGN: A retrospective chart review. SETTING: The Multiple Sclerosis Center at Sheba Medical Center, Israel. PARTICIPANTS: 640 patients with a definite diagnosis of MS. MEASUREMENTS: Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. RESULTS: Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. CONCLUSIONS: Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.

Activities of Daily Living↗
PubMed2001

Asymmetry of fetal cerebral hemispheres: in utero ultrasound study.

BACKGROUND: Slight morphological asymmetry of the cerebral hemispheres has been observed in fetal and newborn brains. In adults, sex differences in hemispheric asymmetry have also been reported. OBJECTIVE: To establish whether cerebral hemisphere asymmetry correlates with sex in fetuses. METHODS: Left-right cerebral hemisphere asymmetry, and the correlation with sex, were studied in 51 male and 51 female fetuses of 20-22 weeks gestation, using diagnostic ultrasound scanning. RESULTS: A total of 102 fetuses were examined. The diameter of the left hemisphere was larger than that of the right, in both female and male fetuses. The mean (SEM) diameter of the left hemisphere was 2.804 (0.174) cm in female fetuses and 2.781 (0.287) cm in male fetuses; the corresponding values for the right hemisphere were 2.627 (0.192) cm and 2.681 (0.267) cm. There was no sex related difference between hemispheric diameters. The interhemispheric difference was significant for both sexes: male fetuses, p = 0.017; female fetuses, p = 0.016. CONCLUSIONS: Left-right fetal brain asymmetry, as measured by in utero ultrasound examination, is apparent at 20-22 weeks gestation regardless of sex.

Brain↗
PubMed2001

Lack of evidence for an association between two genetic polymorphisms in the tumor necrosis factor receptor 1 gene and multiple sclerosis in Ashkenazi Jews.

Multiple sclerosis (MS) is a multifactorial disease with a documented genetic component. Recent experimental models suggested a role for the tumor necrosis factor receptor 1 (TNFR1) in the pathogenesis of the disease. We compared the frequency of two polymorphisms from TNFR1, located in exon 1 and intron 6, in 94 Jewish Ashkenazi MS patients and 83 healthy Ashkenazi controls. No significant differences were observed for both polymorphisms between the patients and the controls. These findings suggest that genetic variants in TNFR1 do not play a significant role in Ashkenazi Jews.

Antigens, CD↗
PubMed2001

Multiple sclerosis in childhood and adolescence: clinical features and management.

The presentation of multiple sclerosis (MS) in childhood has traditionally been thought to be rare. However, more paediatric cases are now being reported, as a result of progress in diagnostic techniques with the use of sensitive imaging modalities of the brain and spinal cord. Management from an early age and the availability of new treatment options have changed the outcome of paediatric MS. Drugs currently available for treatment, such as beta-interferons, copolymer-1 and intravenous immunoglobulin G, have been found to reduce relapse rate, disease severity and progression to disability in adults, but have not been investigated in children and adolescents. The overall outcome of MS in children is apparently no worse than in adults and the disease may even be less aggressive in children. In juvenile MS, disease progression does not appear to be related to age of onset, severity of neurological involvement or mono/polysymptomatic involvement at presentation. The potential to treat MS has significantly changed the prognosis. Early diagnosis is important, as early treatment can prevent or delay the development of disability.

Adolescent↗
PubMed2001

Sex-related differences in the development of the human fetal corpus callosum: in utero ultrasonographic study.

A cross-sectional study of pregnant women presenting for routine fetal ultrasonographic examination was conducted at the Obstetric Ultrasonographic Unit of the Chaim Sheba Medical Center to investigate in utero development of the fetal corpus callosum (CC) in relation to fetal gender. A total of 255 consecutive healthy fetuses of low-risk pregnancies between 16 and 36 weeks' gestation were examined. Thickness and width of the anterior mid-body of the CC were measured in the mid-coronal plane, and length was measured in the mid-sagittal plane. Fetal gender was determined by an independent observer. Female fetuses had statistically significantly thicker CC than males for each gestational age. The mean +/- standard deviation (SD) CC thickness in females was 2.13 +/- 0.8 mm [95% confidence interval (CI) 1.98-2.28] while the mean +/- SD CC thickness in males was 1.8 +/- 0.5 mm (95% CI 1.70-1.89; p < 0.01). The length and width of the CC during gestation did not differ significantly between the sexes. Corpus callosum size as a function of gestational age (GA) in both sexes was expressed by linear regression equations. The correlation coefficients r = 0.93, r = 0.61 and r = 0.62 for length, width and thickness, respectively, in males and r = 0.92, r = 0.71 and r = 0.72 in females were found to be statistically significant (p < 0.01). The present data suggest that female fetuses have a thicker CC than males. These findings support previous studies suggesting sex dimorphism of human CC and raise the possibility that prenatal sex hormones may play a role in determining callosal development.

Corpus Callosum↗
PubMed2000

[Giant lesions in multiple sclerosis--a diagnostic challenge].

Multiple sclerosis is the most common demyelinating disease of the central nervous system affecting young adults, in which destruction of the axon myelin sheath disturbs signal transduction. The disease course is usually remitting and relapsing, but sometimes there is steady neurological deterioration. The diagnosis depends mainly on an adequate clinical history and neurological examination. Evoked potentials, elevated cerebrospinal fluid gamma globulin with oligoclonal bands, and imaging studies, mainly magnetic resonance imaging (MRI), also contribute to the diagnosis. Multiple sclerosis may occasionally present as a mass lesion that clinically and radiologically is indistinguishable from a brain tumor. We present 2 cases of giant tumefactive lesions, proven by brain biopsy to be of demyelinating nature.

Adult↗
PubMed2000

Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis: implications for the treatment of acute relapses of multiple sclerosis.

Dexanabinol (HU-211) is a synthetic non-psychotropic cannabinoid which suppresses TNF-alpha production in the brain and peripheral blood. The effects of dexanabinol in rat experimental autoimmune encephalomyelitis (EAE) were studied using different doses, modes of administration and time regimes. Dexanabinol, 5 mg/kg i.v. given once after disease onset (day 10), significantly reduced maximal EAE score. Increasing the dose or treatment duration resulted in further suppression of EAE. Drug administration at earlier phases during disease induction was not effective. Histological studies supported the clinical findings demonstrating reduction in the inflammatory response in the brain and spinal cord in animals treated with dexanabinol. The results suggest that dexanabinol may provide an alternative mode of treatment for acute exacerbations of multiple sclerosis (MS).

Acute Disease↗
PubMed2000

Multiple sclerosis-from probable to definite diagnosis: a 7-year prospective study.

OBJECTIVES: To investigate the rate of progression from probable to clinically definite multiple sclerosis (MS) and to define patients who had rapidly (within 1 year) progressed to a definite diagnosis. DESIGN: A 7-year prospective study. PATIENTS: A group of 163 patients experiencing their first episode of neurologic symptoms suggestive of MS. All patients had brain magnetic resonance imaging that demonstrated at least 3 demyelinating lesions at onset. RESULTS: Within the follow-up period (mean, 42 months; range, 13-84 months), 136 patients (83.4%) had an additional relapse and were thus defined as having clinically definite MS, whereas 27 patients (16.6%) were defined as having clinically probable MS. Most of the 136 patients with clinically definite MS (57.6%, 94 patients) experienced the additional relapse within 1 year. Demographic and clinical parameters at presentation were analyzed to identify variables predictive of rapid progression (within 1 year) to clinical definite MS. Motor involvement at onset was the only clinical parameter associated with rapid progression to a definite diagnosis. Survival curves demonstrated that polysymptomatic involvement and higher Extended Disability Status Scale score at presentation correlated with rapid progression to definite diagnosis. CONCLUSION: Most patients with a diagnosis of probable MS and positive brain magnetic resonance imaging will progress rapidly to clinically definite MS.

Adolescent↗
PubMed2000

Immunoglobulin treatment in refractory Myasthenia gravis.

Failure to induce and maintain remission in severe exacerbations of myasthenia gravis (MG), despite optimal care, is a common problem. We evaluated the efficacy and safety of high-dose intravenous immunoglobulin (IVIg) therapy in an open-label study of 10 patients with severe generalized myasthenia and an acute deterioration unresponsive to conventional therapy including high-dose corticosteroids, cyclosporine, and azathioprine. Intravenous Ig at a loading dose of 400 mg/kg was administered daily for 5 consecutive days, with maintenance IVIg treatment at a dose of 400 mg/kg, once every 6 weeks. Significant improvement occurred in all patients, beginning at 6 +/- 2 days of treatment as measured by the Osserman scale, fatigue variables, muscle strength, and respiratory function tests. No side effects were observed during induction of remission. Further IVIg treatments were highly efficacious in maintaining the remission. The severity of the disease decreased by 2.5 +/- 0.8 grades of the Osserman scale over a period of 1 year (P <0.001), in parallel with reduction of immunosuppressive therapy as well as a decrease in acetylcholine receptor antibody titers (P < 0.01). Intravenous Ig therapy seems to be highly potent for inducing rapid improvement in refractory myasthenia during acute deterioration as well as for maintaining remission.

Adult↗
PubMed2000

Axial growth of the fetal eye and evaluation of the hyaloid artery: in utero ultrasonographic study.

The aims of this prospective, cross-sectional study were to report axial ocular growth during human gestation, to determine the presence of the hyaloid artery (HA) and its blood flow, and to provide a timetable for HA regression. The study group comprised 231 low-risk singleton pregnancies between 14 and 38 weeks' gestation. Ocular axial length (OAL), anterior chamber depth (ACD) and posterior chamber depth (PCD) were measured using high-resolution ultrasound. The growth of these eye segments in correlation with gestational age (GA) was established. The presence of the HA and its regression were determined. By using power Doppler, ultrasound blood flow within the HA was estimated. HA regression is a gradual process that is not evident before 18 weeks' gestation. In all fetuses beyond 29 weeks' gestation, no HA could be detected (P<0.001). Blood flow within the HA was documented only until the 16th week of gestation. The correlation coefficients, r=0.924, 0.784 and 0.929, for OAL, ACD and PCD, respectively, were found to be highly statistically significant (P<0.0001). The present data offer normative measurements of the fetal axial eye lengths, timetable for HA regression and flow cessation.

Adult↗
PubMed2000

Suppression of experimental autoimmune encephalomyelitis by intravenously administered polyclonal immunoglobulins.

Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats either by active immunization with myelin basic protein (MBP) or by adoptive transfer using anti-MBP specific CD4(+)T cells. Treatment with human polyclonal immunoglobulins (IgG) effectively suppressed active EAE. Time-dependent experiments demonstrated that the effect of IgG was manifested only when treatment was given immediately after immunization; administration from day 7 after disease induction did not suppress the disease. In the adoptive transfer model of EAE, IgG had no effect in vivo. However, pretreatment in vitro of the antigen-specific T-cells with IgG inhibited their ability to mediate adoptive EAE, as it did in active EAE. Similarly, in vitro IgG pretreatment of the antigen-specific T-cells suppressed the proliferative response to MBP. Fluorescent Activated Cell Sorter (FACS) analysis demonstrated the binding of IgG to activated T-cell lines that was inhibited by soluble Fc molecules. The differential effects of IgG on active EAE and on the adoptive transfer of EAE suggest that IgG in vivo can suppress disease by acting during the early phase of the immune response which involves naive T cells. The inhibition of T-cell proliferation and adoptive transfer of EAE by incubation of T cells in vitro appears to require higher concentrations of IgG than those obtained in vivo.

Adoptive Transfer↗
PubMed2000

Quality of life in multiple sclerosis: development and validation of the 'RAYS' scale and comparison with the SF-36.

OBJECTIVE: To develop a self-administered rating scale for quantifying quality of life (QoL) in multiple sclerosis (MS) patients. METHODS: The RAYS scale items were derived from a source of 600 questions composed by our Centre's experts from commonly used instruments that assess physical, psychological, and social-familial dimensions. Prior to finalization of the RAYS QoL, candidate items were administered to 15 health rehabilitation professionals. Clarity, importance, relevance and specificity were graded for each item by every professional independently. Items chosen for the final version were graded as good or excellent on all these aspects. The Medical Outcome Study Short Form-36 (SF-36) was used to compare health appraisal with the RAYS scale. RESULTS: Each of the three subscales of the RAYS covers a different dimension (physical, psychological, and social-familial) and each includes 15 self-report items scored from 1 (best) to 4 (worse), focusing on the preceding week. Validation was achieved through administration of the scale to 50 randomly selected MS patients and to 50 age, sex-, education- and family status-matched healthy controls. All RAYS dimensions among MS patients reached a Cronbach's coefficient alpha > 0.8. Mean values for all dimensions were greater in patients than in controls (P < 0.002). Patients scored below norms for the general population in the majority of the SF-36 subscales (on average 32% lower). Significant correlation was found between the two scales especially in the physical and social functioning subscales. CONCLUSION: The RAYS scale demonstrated high internal consistency and significant discriminative value, and is thus a suitable disease-specific tool for measuring QoL in MS.

Activities of Daily Living↗
PubMed2000

[Intravenous immunoglobulins (IVIg) in the treatment of multiple sclerosis].

Intravenously administered immunoglobulins (IVIg) have been used for the treatment of various autoimmune diseases. In multiple sclerosis (MS), recent studies point out the beneficial role of this treatment that reduces relapse rate and arrests disease progression in relapsing-remitting patients. In the present article, we summarize and interpret the clinical, immunological, and neuro-radiological data related to IVIg treatment in MS. A synthesis between the information gathered will enable better understanding and treatment of this chronic disease.

Disease Progression↗
PubMed2000

Immunoglobulins treatment in multiple sclerosis and experimental autoimmune encephalomyelitis.

Intravenously administered immunoglobulins (IgG) treatment has several modes of action that can regulate the immune response during different steps of the inflammatory process in experimental autoimmune encephalomyelitis (EAE) and Multiple Sclerosis (MS). The immunomodulatory effects IgG are largely dependent on their ability to interact with membrane molecules of lymphocytes and monocytes. Better understanding of these mechanisms of action in relation to the pathogenesis of MS, is important in order to decide the time of initiation and the duration of treatment in MS patients. In order to have the best beneficial effect on disease course, future research should focus on the initial events that activate the disease and on the early treatment modalities of IgG in MS.

Animals↗