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M Freedman

Publications and source records attributed to M Freedman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Different patterns of autobiographical memory loss in semantic dementia and medial temporal lobe amnesia: a challenge to consolidation theory.

Temporally graded retrograde memory loss, with a disproportionate impairment of recent relative to remote memories, is considered a hallmark of medial temporal lobe amnesia. According to consolidation theory, the hippocampal complex, which includes the hippocampal formation, parahippocampal gyrus, the entorhinal and perirhinal cortex, plays a time-limited role in memory, needed only until consolidation in the neocortex is complete (Squire, Psychological Review 1992; 99: 195-231). Recent support for this theory comes from findings of a reverse gradient in people with semantic dementia with neocortical degeneration but a relatively preserved hippocampal complex (Hodges and Graham, Neuropsychologia 1998; 36: 803-25). Consolidation theory is challenged by evidence that remote autobiographical memory is not always spared in amnesia (Nadel and Moscovitch, Current Opinion in Neurobiology 1997; 7: 217-27) and that semantic memory becomes highly personalized in semantic dementia (Snowden et al., Memory 1995; 3: 225-46). According to Nadel and Moscovitch, the hippocampal complex is needed to retain and retrieve detailed memories of autobiographical episodes no matter how old they are. To test consolidation theory against the opposing view, we investigated the role of the hippocampal complex in recent and remote autobiographical and personal semantic memory by contrasting the memory of a semantic dementia patient, EL, with that of an amnesic patient, KC, using family photographs as recall cues. KC demonstrated a complete loss of autobiographical episodes with a sparing of autobiographical facts; EL demonstrated well-preserved memory for episodes with a reverse gradient for personally relevant names. The influence of autobiographical significance on memory for names of public figures was examined further by comparing the effect that familiarity and recollection had on recognition of names of famous people and famous places. EL's memory was influenced by autobiographical significance, whereas KC's was not. We propose that the hippocampal complex plays a permanent role in the storage and retrieval of autobiographical episodes and that autobiographical significance may affect semantic representations.

Aged↗
PubMed2001

Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: potential role of cytokines in clinical manifestations.

A permanent cell line, HSC-M1, was established from a child with advanced CD30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features included irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, neutrophilia, and bone marrow erythrophagocytosis. While HSC-M1 cells exhibited an immunophenotype characteristic of ALCL of T-cell lineage, the cell line also demonstrated features of monocyte-macrophage lineage. Cytogenetic and polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and involved bone marrow demonstrated the characteristic non-random chromosomal translocation t(2:5)(p23:q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immunosorbent assays showed increased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M1 cells of some of these cytokines was demonstrated, the production of others was only detectable after stimulation with exogenous CD30 ligand. With few exceptions, there was good correlation between serum cytokine levels and cytokines produced by HSC-M1 cells. These findings indicate that cytokine production is a feature of ALCL cells and that some of the clinical manifestations in ALCL may result from cytokines produced by either the malignant or accessory cells.

Chromosomes, Human, Pair 2↗
PubMed2001

Quantifying qualitative features of Block Design performance among healthy older adults.

Block Design tasks are neuropsychologically valuable, but standard scoring sacrifices potentially useful information that could elucidate the cognitive processes underlying performance failures. Qualitative indices that were proposed in the WAIS-R-NI [Kaplan, E., Fein, D., Morris, R., & Delis, D. (1991). The WAIS-R as a neuropsychological instrument [Manual]. San Antonio, TX: Psychological Corporation] should help to remedy this situation but have received little research attention. We present WAIS-R Block Design data for 177 healthy older adults (aged 50-90) incorporating several qualitative measures, outlining normative ranges and examining age differences. Proportional scoring, counts of single-block placement and rotation errors, counts of parameter-violating errors such as breaking configuration, and availability of implicit grid information all offer potentially valuable supplementary data that can enrich clinical interpretation of Block Design protocols.

Journal Article↗
PubMed2000

Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation.

Severe congenital neutropenia (CN) (Kostmann syndrome) is a hematologic disorder characterized by a maturation arrest of myelopoiesis at the promyelocyte/myelocyte stage of development. This arrest results in severe neutropenia leading to absolute neutrophil counts (ANC) below 0.2 x 10(9)/L associated with severe bacterial infections from early infancy. Data on over 300 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) beginning in 1994 indicate that more than 90% of these patients respond to recombinant human granulocyte-colony stimulating factor (r-HuG-CSF) treatment with an ANC greater than 1. 0 x 10(9)/L. For patients who are refractory to r-HuG-CSF treatment and continue to have severe and often life-threatening bacterial infections, hematopoietic stem cell transplantation is the only currently available treatment. We report on a total of 11 patients with CN reported to the SCNIR who underwent transplantation for reasons other than malignant transformation between 1976 and 1998. Of these patients, 8 were nonresponders or showed only partial response to r-HuG-CSF treatment with ongoing infections. Results from these patients suggest that transplantation of stem cells from an HLA-identical sibling is beneficial for patients refractory to r-HuG-CSF. (Blood. 2000;95:1195-1198)

Adolescent↗
PubMed2000

Announcements

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Journal Article↗
PubMed2000

Announcements

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Journal Article↗
PubMed2000

Speed and memory in WAIS-R-NI Digit Symbol performance among healthy older adults.

Although roles have been proposed for both graphomotor speed and learning in the execution of Digit Symbol, few data have been available concerning performance across the adult lifespan on the Symbol Copy, paired associates, or free recall measures derived from Digit Symbol and recommended in the WAIS-R-NI. We report findings on 177 healthy older adults (ages 50-90), providing normative data by age group, education level, and gender. As previously reported, Digit Symbol scores decline steeply with age (r = -.64). Symbol Copy speed declines almost as steeply (r = -.58). Incidental learning, however, declines only modestly (r = -.26 on both measures). Symbol Copy is a far stronger correlate of Digit Symbol (r = .72) than are paired associates or free recall (r = .26 and r = .28, respectively). The 2 incidental learning measures do, however, offer valuable supplementary information as part of a comprehensive individual assessment. When low Digit Symbol scores are produced by slowing on Symbol Copy, further evaluation of perceptual and motor speed and dexterity are indicated. When low incidental learning scores are obtained, further evaluation of memory is warranted. Qualitative analysis of errors (e.g., rotations) made on the incidental learning procedures may also be valuable.

Adult↗
PubMed2000

Matched unrelated bone marrow transplantation for combined immunodeficiency.

Bone marrow transplantation (BMT) from siblings is the treatment of choice for severe combined immunodeficiency (SCID). The objective of this study was to evaluate the efficiency of BMT from matched unrelated donors (MUD) in congenital immunodeficiencies when a sibling donor is unavailable. Sixteen consecutive patients with SCID (n = 9) and CID (n= 7), were referred for an unrelated donor search. Acceptable donors were found for all patients. Fifteen patients received busulfan and cyclophosphamide pretransplant conditioning. One patient had an early loss of graft and was reconditioned using cyclophosphamide and total body irradiation. The graft-versus-host disease (GVHD) prophylaxis used was methylprednisolone, cyclosporin A with or without methotrexate. Neutrophil engraftment was rapid and was achieved in all patients within a mean of 15.4 days. Only 13 episodes of fever were recorded shortly after BMT. GVHD of grade II or more was apparent in 2/9 (22%) of SCID patients and in 4/7 (57%) of CID patients. Overall survival was 75% with a mean follow-up of 47.4 months (range 18-101). Six out of nine SCID patients (67%) and 6/7 (86%) of CID patients are alive and well. Eleven patients had normal humoral immunity, and cell-mediated immunity as measured by flow cytometry and mitogenic responses, was intact in all patients. Intradermal candida skin test was positive in 9/10 patients tested. We conclude that BMT from MUD results in rapid engraftment and is therefore associated with a low rate of infection contributing to the improved survival rate. The protocol used is especially favorable for patients with combined immunodeficiency.

Anti-Bacterial Agents↗
PubMed2000

Normal patterns on 99mTc-ECD brain SPECT scans in adults.

UNLABELLED: Normative ethyl cysteinate dimer (ECD) SPECT data must be available to successfully apply ECD SPECT to clinical studies. The purpose of this study was to determine ECD SPECT scan patterns of healthy adults. METHODS: Forty-eight healthy volunteers (22 men, 26 women; age range, 22-95 y; mean age, 47.6 +/- 19.2 y) underwent high-resolution ECD SPECT. For visual analysis of regional brain ECD uptake, we used a scale of +3 to -3, in which +3 and -3 indicated highest ECD uptake and deficit, respectively. For quantitative analysis, we measured the region-to-cerebellum ratio (R/CE) and the region-to-cerebral cortex ratio (R/CO) for 17 regions (13 cortical, 3 subcortical, and 1 cerebellar). RESULTS: On visual analysis, no subject had a score of -3. All subjects had a score of -2 for the hippocampus and a score of +3 for the medial occipital cortex, except for 2 subjects who had a score of +3 for the striatum and thalamus. A frontal eye field and posterior parieto-occipital junction were identified in 60% of subjects with a score of +1 and 79% of subjects with a score of +2. On quantitative analysis, a significant regional variation (ANOVA, P < 0.0001) was seen in R/CE, ranging from 0.709 (hippocampus) to 1.26 (medial occipital cortex). However, regional right-to-left differences and intersubject variability of R/CE were small (asymmetry index, 3.6% +/- 0.8%; coefficient variation, 6.6% +/- 0.7%). R/CE declined significantly with age in 6 regions, including the anterior and posterior cingulate cortex, superior prefrontal and parietal cortex, striatum, and hippocampus (1.0%-2.0% per decade, P < 0.05), whereas R/CO in the cerebellum increased significantly with age (1.0% per decade, P < 0.05). CONCLUSION: Although regional ECD brain perfusion patterns vary significantly, including variability caused by the age-related effect, intersubject variability is small. Recognition of these normal patterns is important for clinical interpretation of ECD SPECT studies.

Adult↗
PubMed2000

Vitamin B12 deficiency and incontinence in older people.

OBJECTIVES: To investigate the relationship between urinary incontinence and Vitamin B12 deficiency in community-living older people using standard serum cobalamin levels as well as the metabolites methylmalonic acid (MMA) and total homocysteine (HCYS). DESIGN: A prospective cross-sectional study of community-living older people. PARTICIPANTS: Independent and cognitively normal adults (mean age=72 years, range=65-89 years) living in the community. One hundred and nineteen volunteers were recruited at group meetings, activity groups, and through the use of posters. MEASUREMENTS: Information on urinary continence was provided by the participant during a systematic medical history, and was defined as any amount of uncontrolled leakage of urine. Vitamin B12, methylmalonic acid and homocysteine levels were determined in all subjects. MAIN RESULTS: We found no significant differences between the continent and incontinent group in regard to their serum Vitamin B12 (OR=1.34, CI: 0.39-4.58, p=.424), methylmalonic acid levels (OR=0.71, CI: 0.24-2.10, p=.386), or total homocysteine levels (CI: 0.29-4.54, p=.535). CONCLUSIONS: In our study continence was not significantly affected by the B12 status of the subject; neither serum B12 levels or the metabolites MMA and HCYS (reflecting B12 function) were significantly different in the continent group versus the incontinent one.

Aged↗
PubMed1999

Close relationship between systemic lupus erythematosus and thrombotic thrombocytopenic purpura in childhood.

OBJECTIVE: To determine the association between childhood-onset thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE). METHODS: The charts of all 5 patients diagnosed with idiopathic TTP at the Hospital for Sick Children (HSC) in Toronto from 1975 to 1998, and all cases of childhood-onset TTP (ages 6-20 years) reported in the literature over the same period were reviewed. Fourteen of the 44 patients identified in the literature were excluded from the analysis for lack of clinical and laboratory information. The remaining 35 patients were grouped into either an SLE/TTP group or a TTP only group, according to the presence or absence of the American College of Rheumatology (ACR) classification criteria for SLE. The groups were compared for differences in clinical or laboratory features. RESULTS: The clinical presentation and initial disease course of pediatric patients with TTP were similar to those observed in adults. Of the 35 patients with childhood-onset TTP included in this review, 9 (26%) fulfilled > or = 4 ACR criteria for SLE and 8 (23%) were found to have incipient SLE. Of the 5 patients initially diagnosed with idiopathic TTP at the HSC, 3 were diagnosed with SLE within 3 years, and the other 2 patients fulfilled 3 ACR classification criteria for SLE within 4 years of disease onset. The clinical syndrome of pediatric TTP presenting with proteinuria, especially with high-grade proteinuria, was significantly associated with the development or coexistence of childhood-onset SLE. CONCLUSION: TTP in childhood is a rare, but life-threatening, disease. Unlike in adults, TTP in childhood is commonly associated with SLE. High-grade proteinuria at diagnosis of TTP is the best predictor for the presence or subsequent development of SLE.

Adolescent↗
PubMed1999

Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar.

OBJECTIVES: With the use of clinical data from a large international cohort, we evaluated and compared affected siblings and isolated cases. STUDY DESIGN: Data from 116 families were collected, and patients conforming to our predetermined diagnostic criteria were analyzed. Phenotypic manifestations of affected siblings and singletons were compared with the use of t tests, Wilcoxon scores, and chi2 analysis. RESULTS: Eighty-eight patients (33 female, 55 male; median age 5.20 years) fulfilled our predetermined diagnostic criteria for Shwachman syndrome; 63 patients were isolated cases, and 25 affected siblings were from 12 multiplex families. Steatorrhea was present in 86% (57 of 66), and 91% (78 of 86) displayed a low serum trypsinogen concentration. Patients older than 4 years more often had pancreatic sufficiency. Neutropenia occurred in 98%, anemia in 42%, and thrombocytopenia in 34%. Myelodysplasia or cytogenetic abnormalities were reported in 7 patients. Short stature with normal nutritional status was a prominent feature. CONCLUSIONS: Clinical features among patients with Shwachman syndrome varied between patients and with age. Similarities in phenotype between isolated cases and affected sibling sets support the hypothesis that Shwachman syndrome is a single disease entity.

Bacterial Infections↗
PubMed1999

Telomere shortening in leucocyte subsets of long-term survivors of allogeneic bone marrow transplantation.

Recent studies have demonstrated excessive telomeric shortening in peripheral blood leucocytes of bone marrow transplant (BMT) recipients. This finding has raised concerns about accelerated haemopoietic ageing that might predispose to clonal disorders and late graft failure. We studied the peripheral blood neutrophils and T cells of 14 fully engrafted long-term survivors of BMT. We found that in both neutrophils and T cells there was significant telomere shortening in the recipient (0.6 and 0.5 kb, respectively; P < 0.001 and < 0.04, respectively). We found no relationship between degree of shortening and the nucleated cell dose given at the time of transplant. We also demonstrated significantly longer telomeres in T cells than neutrophils from the same individual (mean 11.6 kb and 10.6 kb, respectively; P=0.0001). We propose mechanisms to account for these observations. The replicative stress that causes this telomere shortening does not necessarily occur at the level of the most primitive haemopoietic stem cell.

Adolescent↗
PubMed1999

Information Multiple Choice among healthy older adults: characteristics, correlates, and clinical implications.

Information Multiple Choice (WAIS-R-NI, Kaplan et al., 1991), may be valuable when used in conjunction with the standard Information subtest. Due to the reduced retrieval demands posed by its recognition format, scores should be even less susceptible to neuropathology or normal aging than are those on the standard (recall) test, facilitating assessment of premorbid attainment in individuals suffering from retrieval-related memory deficits. We provide reliability, validity, and normative data on Information Multiple Choice from a sample (N = 177) of healthy adults aged 50 - 90 years. Information Multiple Choice correlates strongly with the standard Information subtest (r = .81) and, as predicted and unlike the standard test, does not decline even in very old age. The construct validity of Information Multiple Choice is supported, and its clinical utility will be enhanced by these normative data.

Adult↗
PubMed1999

A neuropsychological comparison of demented and nondemented patients with Parkinson's disease.

The strength and sensitivity of neuropsychological test findings in patients with Parkinson's disease (PD) was reviewed using meta-analytic principles to provide a basis of comparison of deficits in nondemented and demented patients with PD. The review revealed significant relationships among duration of disease, physical disability, and cognitive impairment in nondemented patients, and qualitative and quantitative differences in the pattern of neuropsychological test impairments between nondemented and demented patients with PD. The disparate profiles of neuropsychological impairment in nondemented and demented patients may indeed reflect disease progression in keeping with the significant clinical correlations in nondemented patients. That is, as the duration of the disease endures, it appears that performance on tasks of delayed recall deteriorates first, followed by performance on measures of manual dexterity, cognitive flexibility, and abstraction.

Adult↗