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Biomedical subjects

M A Elliott

Publications and source records attributed to M A Elliott.

At least 19 recordsLinked to original sources
PubMed2000

Evidence for 40-Hz oscillatory short-term visual memory revealed by human reaction-time measurements.

Four experiments show that presentation of a synchronous premask frame within a 40-Hz, flickering premask matrix primes subsequent detection of a Kanizsa-type square by generation of a 40-Hz prime. Reaction time (RT) priming effects indicated a 150-200-ms prime duration following premask display. RTs were also found to be sensitive to the phase relationship between offset of the premask display relative to the onset time of the target: Priming effects were maximal when the target was presented out of phase with premask presentation (i.e., at interstimulus intervals displaced by 180 degrees relative to the 40-Hz rhythm of premask-frame presentation). Taken together, these results demonstrate the existence of a very short-term visual memory that oscillates at 40 Hz. The findings are discussed in the context of complementary psychological and neurophysiological findings related to visual-object coding and the role of gamma-band activity in the brain.

Adult↗
PubMed1999

Spectral quantitation by principal component analysis using complex singular value decomposition.

Principal component analysis (PCA) is a powerful method for quantitative analysis of nuclear magnetic resonance spectral data sets. It has the advantage of being model independent, making it well suited for the analysis of spectra with complicated or unknown line shapes. Previous applications of PCA have required that all spectra in a data set be in phase or have implemented iterative methods to analyze spectra that are not perfectly phased. However, improper phasing or imperfect convergence of the iterative methods has resulted in systematic errors in the estimation of peak areas with PCA. Presented here is a modified method of PCA, which utilizes complex singular value decomposition (SVD) to analyze spectral data sets with any amount of variation in spectral phase. The new method is shown to be completely insensitive to spectral phase. In the presence of noise, PCA with complex SVD yields a lower variation in the estimation of peak area than conventional PCA by a factor of approximately 2. The performance of the method is demonstrated with simulated data and in vivo 31P spectra from human skeletal muscle.

Analysis of Variance↗
PubMed1999

Chronic lymphocytic leukaemia with symptomatic diffuse central nervous system infiltration responding to therapy with systemic fludarabine.

B-cell chronic lymphocytic leukaemia is an indolent disease characterized by the insidious accumulation of small mature-appearing lymphocytes in the peripheral blood, bone marrow and lymphoid tissues. Direct symptomatic invasion of the central nervous system is exceedingly rare and, to our knowledge, only three cases histologically confirmed as true chronic lymphocytic leukaemia have been reported in the literature. We describe the first case of early Rai stage B-cell chronic lymphocytic leukaemia presenting with symptomatic infiltration of the brain and spinal cord which could be demonstrated radiographically by magnetic resonance imaging. The diagnosis was confirmed by examination of peripheral blood, cerebrospinal fluid, brain and bone marrow biopsies, both morphologically and immunophenotypically by means of flow cytometric analysis. The patient demonstrated a complete response to therapy with standard-dose systemic fludarabine and remains in complete remission 6 months after completion of therapy.

Antineoplastic Agents↗
PubMed1999

Splenic irradiation in myelofibrosis with myeloid metaplasia: a review.

Morbidity from myeloid metaplasia and myelofibrosis arises from progressive anemia and abdominal discomfort related to massive splenomegaly, which may be associated with hypercatabolic symptoms. To date, no therapy, other than allogeneic bone marrow transplantation, has been shown to cure or to prolong the survival of these patients. Thus, current management strategies are palliative and include red cell transfusional support and androgen therapy for anemia; chemotherapeutic agents for control of thrombocytosis, leukocytosis, and hypermetabolic symptoms; and splenectomy or splenic irradiation for symptomatic splenomegaly. The major indication for splenic irradiation is left upper quadrant discomfort related to massive splenomegaly, usually in patients for whom splenectomy is contraindicated or has been declined. In most patients, it provides relief from abdominal pain and a moderate reduction in splenic size. Although responses are transient, some patients may experience prolonged relief. Splenic irradiation can result in prolonged myelosuppression in certain patients. This calls for cautious dosing, because individual sensitivity is variable and cannot be predicted. The use of splenic irradiation does not preclude subsequent splenectomy; however, the increased risk of postoperative hemorrhage should discourage consideration of splenic irradiation as an alternative or a temporizing measure before splenectomy when indicated.

Humans↗
PubMed1998

Longitudinal study of skeletal muscle adaptations during immobilization and rehabilitation.

This study describes the metabolic, morphologic, neurologic, and functional adaptations observed in the plantar flexors during 8 weeks of lower leg immobilization and 10 weeks of physical therapy following ankle surgery. A combination of magnetic resonance imaging and spectroscopy, isokinetic and isometric muscle testing, and simple functional tests revealed many adaptive changes due to immobilization, including atrophy, loss of muscle strength, reduced central activation, increase in fatigue resistance, and an increase in inorganic phosphate content. After 10 weeks of physical therapy all alterations were reversed, with the exception of a remaining 5.5% deficit in total muscle cross-sectional area.

Adult↗
PubMed1998

Fast imaging of phosphocreatine using a RARE pulse sequence.

A technique is described for acquiring phosphocreatine (PCr) images of skeletal muscle using a rapid acquisition with relaxation enhancement (RARE) pulse sequence. All of the phosphorus metabolites other than PCr are forced to dephase within the first few echoes, whereas the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence maintains a high PCr signal long enough to acquire 64 echoes in a single shot. Axial PCr images of a human forearm with a signal-to-noise ratio of 9 were acquired in 2 min. The effect of the refocusing pulse section profile on the ratio of desired to undesired metabolite signal is demonstrated.

Forearm↗
PubMed1998

Improved resolution and signal-to-noise ratio in MRI via enhanced signal digitization.

The high frequency k-space data in magnetic resonance imaging is often poorly reproduced due to the finite dynamic range of an analog-to-digital converter. The magnitude of this digitization error can equal and even exceed the magnitude of the thermal noise. Under such conditions, attempts to increase image signal-to-noise ratio via signal averaging meet with diminishing success. Because the relative size of the digitization error increases at higher spatial frequencies, a reduction in image resolution is incurred as well. By adjusting the level of the analog signal sampled by the analog-to-digital converter during the course of an imaging experiment, the magnitude of the digitization artifact can be greatly reduced. The results of simulations and imaging experiments are presented which demonstrate that this strategy improves both the signal-to-noise ratio and resolution of magnetic resonance images.

Artifacts↗
PubMed1998

Generalized reciprocity.

The remarkable theorem of reciprocity as described by D. I. Hoult and R. E. Richards (J. Magn. Reson. 24, 71 (1976)) may be generalized to account for the near, intermediate, and radiation zone fields of a magnetic dipole. This form of reciprocity may be important when the wavelength of the NMR signal is not large compared to the distance scale of the system. In these situations the effects of interference may be significant. In addition, both the frequency dependence and distance dependence of the NMR signal amplitude are altered. In general, the distance dependence of the signal follows a weighted sum of 1/r3, 1/r2, and 1/r dependence. The frequency dependence of the signal amplitude is a function of omega, omega2, and omega3. Finally, the signal reflects the full vector field nature of the magnetic dipole. The mathematical expression of generalized reciprocity is completely equivalent to that of Hoult and Richards if the appropriate retarded potential form of the magnetic field is utilized.

Algorithms↗
PubMed1998

Splenic irradiation for symptomatic splenomegaly associated with myelofibrosis with myeloid metaplasia.

Twenty-three patients who had myelofibrosis with myeloid metaplasia (MMM) were treated at our institution with 50 courses of splenic irradiation (SI) for symptomatic splenomegaly. The median dose of radiation per course was 277.5 cGy, administered in a median of 7.5 fractions. 8/23 patients received multiple courses of SI. Of 49 evaluable courses of SI, 46 (93.9%) resulted in an objective decrease in spleen size. The median duration of response was 6 months (range 1-41). Reduction in spleen size was associated with symptomatic relief in all patients. Overall median survival after SI was 22 months. Significant cytopenia occurred in 10 (43.5%) patients, or 16 (32%) of the 50 courses of SI. Prolonged, life-threatening pancytopenia after a single course of SI occurred in six patients (26%), resulting in fatal sepsis or haemorrhage in three (13%). Nine patients underwent subsequent splenectomy: the perioperative mortality rate was 11%. One third of patients experienced postoperative intra-abdominal haemorrhage necessitating surgical re-exploration. SI can provide symptomatic relief and a reduction in spleen size in most MMM patients. The increased risk of postoperative bleeding in patients requiring subsequent splenectomy dictates against considering SI as an alternative to splenectomy for patients who are otherwise good surgical candidates.

Adult↗
PubMed1997

Investigation into the concanavalin A reactivity, fucosylation and oligosaccharide microheterogeneity of alpha 1-acid glycoprotein expressed in the sera of patients with rheumatoid arthritis.

alpha 1-Acid glycoprotein (AGP) exists as an heterogeneous population of glycosylated variants (glycoforms) in plasma. The concentration of AGP increases some 2-5 fold in certain pathophysiological states exemplified by the chronic inflammatory disease, rheumatoid arthritis (RA). Moreover, the expressed glycosylation pattern alters in such conditions, indicating functional significance that is likely to be related to the oligosaccharide heterogeneity. We have investigated the heterogeneity of AGP glycosylation using the technique of high pH anion-exchange chromatography (HPAEC). AGP was isolated from the blood of RA sufferers, partially separated by Concanavalin A (Con A) affinity chromatography into bound and non-bound fractions and was enzymatically deglycosylated. Chromatography on the pellicular HPAE resin at pH 13 separated the released oligosaccharides and allowed a comparison of profiles in terms of branching and fucosylation. Results demonstrate an abnormal RA AGP glycosylation, with a tendency towards tri- and tetra-antennary oligosaccharides and enhanced fucosylation, in addition to the possible existence of penta-sialylated RA AGP glycoforms.

Arthritis, Rheumatoid↗
PubMed1997

Volumetric measurement of human calf muscle from magnetic resonance imaging.

Muscle mass is a determining factor in skeletal muscle function and is affected by inactivity, immobilization, disease, and aging. The aim of this study was to develop an objective and time-efficient method to quantify the volume and cross-sectional area of human calf muscles using three-dimensional magnetic resonance images. We have estimated the errors incurred in muscle volume measurements arising from artifacts known to occur in magnetic resonance imaging (MRI). The largest source of error was due to partial volume effects, which resulted in overestimation of phantom volumes ranging from 145 to 900 cc by 6% to 13%. The magnitude of this effect has been shown to increase with decreasing object size and decreasing spatial resolution. We have presented a straightforward correction for this effect, which has reduced the volume measurement error to less than 4% for all cases. Through the use of computer simulations, the correction algorithm has been shown to be independent of object shape and orientation. To reduce user subjectivity, a semiautomated computer program has been developed to segment MRI data for particular muscle groups. Images from seven human subjects were analyzed by the program, yielding muscle volumes of 154.2 +/- 23.2, 281.2 +/- 35.8, and 432.2 +/- 83.7 for the lateral gastrocnemius, medial gastrocnemius, and soleus, respectively.

Adult↗
PubMed1997

New drugs in essential thrombocythemia and polycythemia vera.

Among the chronic myeloproliferative disorders, polycythemia vera and essential thrombocythemia are unique because of their association with thrombohemorrhagic manifestations and their relatively indolent clinical course. Patients with essential thrombocythemia may not have a significant shortening of life-expectancy and most may not require specific therapy. However, patients with polycythemia vera have a significant risk of transformation of polycythemia vera into acute leukemia or postpolycythemic myelofibrosis (or both). 'High-risk-for-thrombosis' patients with either polycythemia vera or essential thrombocythemia require specific therapy with a platelet-lowering agent to prevent thrombotic complications. Currently, the standard agent used for this is hydroxyurea. However, its tetratogenic and leukemogenic potential has been of concern. As a result, new platelet-lowering agents are being evaluated in the treatment of polycythemia vera and essential thrombocythemia. Anagrelide and interferon alfa are two such agents and have been shown to be effective in reducing platelet counts in patients with chronic myeloproliferative disorders. The putative mechanism of action of these drugs, their specific activity in polycythemia vera and essential thrombocythemia, side-effect profile, and current indications are discussed herein.

Antineoplastic Agents↗
PubMed1997

Interferon-alpha therapy in polycythemia vera and essential thrombocythemia.

Essential thrombocythemia (ET) and polycythemia vera (PV) are chronic clonal myeloid disorders that originate from the multipotential hematopoietic stem cell. They are characterized, respectively, by excessive thrombocytosis and erythrocytosis, a high incidence of thrombohemorrhagic events, vasomotor symptoms, and an inherent tendency to undergo leukemic transformation. Current standard therapies to control the excess accumulation of myeloid cells and to provide symptomatic relief carry either a persistent risk of thrombosis, as in the case of phlebotomy, or, in the case of hydroxyurea, the potential for inducing leukemia. None alter the natural history of these diseases. Interferon-alpha has been shown to have potent antiproliferative effects on the hematopoietic stem cells and bone marrow fibroblasts and, as a result, has received much attention as a therapeutic agent for chronic myeloproliferative disorders. The ability of interferon-alpha to induce hematologic and cytogenetic remission in chronic phase chronic granulocytic leukemia has further increased interest in this agent. Interferon-alpha has shown therapeutic activity in PV and ET, as demonstrated in multiple small studies and single-arm trials reviewed in this article. Reported beneficial effects include the ability to control excessive erythrocytosis and thrombocytosis and such disease-related features as vasomotor symptoms, pruritus, and splenomegaly. Recent reports of cytogenetic remission and reversal of bone marrow fibrosis after interferon therapy are of interest. Advantages over current therapeutic standards include lack of known leukemogenic and teratogenic effects and the potential to alter the underlying course of disease. Nevertheless, none of the information available allows definite therapeutic recommendations for the use of interferon-alpha in PV or ET. The available data support the need for randomized controlled trials comparing interferon-alpha with standard therapy.

Cell Division↗
PubMed1996

Familial hemiplegic migraine, nystagmus, and cerebellar atrophy.

Familial hemiplegic migraine (FHM) is an autosomal dominant disorder characterized by transient hemiplegia during the aura phase of a migraine attack. Nystagmus has been reported in individuals affected with this disorder, but the origin of the ocular motility findings is unknown. A three-generation family with FHM is described and clinical histories are outlined. Ocular motility evaluations were performed on 7 family members, 5 with a history of hemiplegic migraine and 2 without history of migraine. All affected family members had abnormal eye movements consistent with vestibulocerebellar dysfunction. Magnetic resonance imaging scans in affected family members revealed cerebellar vermian atrophy. DNA linkage analysis revealed a common marker in all the affected family members on chromosome 19. We suggest that the hemiplegic migraine attacks and the cerebellar degeneration are linked genetically and that the eye movements are not the ischemic sequelae of recurrent migraine. Strikingly similar ocular motility findings and cerebellar degeneration are reported in both FHM and a genetically related disorder, hereditary paroxysmal cerebellar ataxia (HPCA). The significance of these similarities is discussed along with a proposed pathophysiology for FHM.

Adolescent↗