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Biomedical subjects

Patricia K Coyle

Publications and source records attributed to Patricia K Coyle.

9 recordsLinked to original sources

High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis.

BACKGROUND: High-dose cyclophosphamide is active in immune-mediated illnesses. OBJECTIVE: To describe the effects of high-dose cyclophosphamide on severe refractory multiple sclerosis. DESIGN, SETTING, AND PATIENTS: Patients with multiple sclerosis with an Expanded Disability Status Scale (EDSS) score of 3.5 or higher after 2 or more Food and Drug Administration-approved disease-modifying therapy regimens were evaluated. INTERVENTIONS: Patients received 200 mg/kg of cyclophosphamide over 4 days. MAIN OUTCOME MEASURES: Patients had brain magnetic resonance imaging and neuro-ophthalmologic evaluations every 6 months and quarterly EDSS and quality-of-life evaluations for 2 years. RESULTS: Twelve patients were evaluated for clinical response (median follow-up, 15.0 months; follow-up range, 6-24 months). During follow-up, no patients increased their baseline EDSS scores by more than 1.0. Five patients decreased their EDSS scores by 1.0 or more (EDSS score decrease range, 1.0-5.0). Two of 11 patients had a single enhancing lesion at baseline; these lesions resolved after high-dose cyclophosphamide treatment. At 12 months, 1 patient showed 1 new enhancing lesion without a corresponding high-intensity T2-weighted or fluid-attenuated inversion recovery signal. Patients reported improvement in all of the quality-of-life parameters measured. Neurologic improvement involved changes in gait, bladder control, and visual function. Treatment response was seen regardless of the baseline presence or absence of contrast lesion activity. Patient quality-of-life improvement occurred independently of EDSS score changes. In this small group of patients with treatment-refractory multiple sclerosis, high-dose cyclophosphamide was associated with minimal morbidity and improved clinical outcomes. CONCLUSIONS: High-dose cyclophosphamide treatment in patients with severe refractory multiple sclerosis can result in disease stabilization, improved functionality, and improved quality of life. Further studies are necessary to determine the most appropriate patients for this treatment.

Adult↗

Recent advances in the neuroimaging of multiple sclerosis.

Neuroimaging studies continue to provide important insights into the central nervous system disease pathology of multiple sclerosis (MS). Although conventional magnetic resonance imaging remains the mainstay of diagnosis and laboratory assessment of therapeutic response in MS, quantitative techniques continue to extend our understanding of both macroscopic and microscopic disease processes. Over the past year, many published studies have investigated measures of brain atrophy, gray matter involvement, vascular properties, and myelin and neuronal loss and have examined their relationship to clinical disease expression, genotype, and therapy. An important trend continuing over the past year is the development of targeted agents to improve the pathologic specificity of imaging measures. Specific disease measures such as endothelial activation, microglial activation, and cell trafficking are accessible to neuroimaging and offer significant promise for improved characterization of central nervous system involvement in MS.

Animals↗

Increased serum neopterin levels in adults with Down syndrome.

We quantitated serum neopterin levels in Down syndrome (DS), normal controls, Alzheimer's disease, multiple sclerosis and other neurological diseases. We then analyzed the relationships with age, sex, apolipoprotein E (Apo E) phenotype, and amyloid beta protein 1-40 (Abeta40) and 1-42 (Abeta42) levels. Neopterin levels were higher in DS than all other groups. Levels in young DS (< 40 years of age) and old DS (> 41 years) were similar. There was no significant correlation between neopterin levels and age, sex, Apo E phenotype, and Abeta40 or Abeta42 levels in DS. This lack of correlation between neopterin and Abeta levels suggests that the higher neopterin concentrations in DS group reflect inflammatory cell activation rather than AD neuropathology.

Adult↗

Gender issues.

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Animals↗

Preferential presence of decorin-binding protein B (BBA25) and BBA50 antibodies in cerebrospinal fluid of patients with neurologic Lyme disease.

Borrelia burgdorferi antibodies preferentially present in cerebrospinal fluid (CSF) were examined by differentially probing a B. burgdorferi expression library with CSF and sera from patients with neurologic Lyme disease. Several phage clones selectively reacted with CSF, and these genes were then expressed in recombinant form and used to detect specific antibody in an enzyme-linked immunosorbent assay. Decorin-binding protein B (BBA25) and BBA50 (hypothetical protein) elicited immunoglobulin G (IgG) or IgM detectable in CSF-but not sera-of patients, demonstrating preferential antibody production during neuroborreliosis.

Adhesins, Bacterial↗

Normative data for the selective reminding test: a random digit dialing sample.

Healthy control participants (46 women, M age=44.3 yr., SD=7.6; 29 men) were recruited to undergo a comprehensive neuropsychological battery and serve as a comparison group in a study of cognitive functioning in patients with Lyme isease. Participants were selected using Mitofsky-Waksberg random digit dialing. The Buschke 12-word, six-trial Selective Reminding Test was administered as part of the neuropsychological battery and normative data are presented stratified by age and sex. Performance on alternate forms of this measure were examined. Mean education, intelligence quotient, and Wide Range Achievement Test-3 Reading scores are reported.

Achievement↗

Human T lymphocyte response to Borrelia burgdorferi infection: no correlation between human leukocyte function antigen type 1 peptide response and clinical status.

We tested the hypothesis that cross-reactivity between the outer surface protein A (OspA) of Borellia burgdorferi and human leukocyte function antigen (LFA) type 1 mediates chronic autoimmune sequelae of Lyme disease. T cell response was studied in subjects with Lyme disease presenting with erythema migrans alone (n=36), erythema migrans with neurological disease (n=12), and chronic Lyme disease syndrome (n=20), as well as healthy control subjects from Lyme-endemic (n=50) and -nonendemic (n=18) regions. Antigens included recombinant OspA and OspC (all strain B31) and human LFA-1 peptide (IYVIEGTSKQDLTSF). Proliferation to OspA was detected in 11 (28%) of 39 of subjects presenting with erythema migrans, which increased to 50% at 4 weeks of follow-up. Reactivity to OspA and LFA-1 was significantly correlated (P<.001) and was observed in 18 (78%) of 23 of OspA-responsive subjects. However, there was no correlation between T cell response to human LFA-1 peptide and clinical status.

Adolescent↗

Lyme disease.

Lyme disease is due to infection with a tick-borne spirochete, Borrelia burgdorferi. Risk for infection is confined to regions that contain the Ixodid tick vector. Characteristic skin, musculoskeletal, cardiac, ocular, and neurologic disorders are associated with the local, early dissemination and late stages of infection. Neurologic involvement can be seen at all stages, and involves both central and peripheral nervous system syndromes. The inability to easily culture B. burgdorferi and the lack of a reliable active infection assay have contributed to controversies in diagnosis and management. Because the vast majority of patients are seropositive, however, antibody testing is helpful to support the diagnosis of Lyme disease. With appropriate antibiotics, most patients do well. This infection provides an important model system to understand how interactions between an organism, vector, and host lead to disease. It also provides a model to study how infectious agents lead to neurologic disease.

Animals↗

Issues and practices in multiple sclerosis.

The objective of this roundtable discussion of experts in the field of multiple sclerosis (MS) was to summarize the current understanding of MS and its therapeutic options. The experts discussed subjects ranging from the etiology of MS to the current standards for patient care. Specific topics included the subtypes of MS, with a focus on the benign subtype, brain atrophy, the role of magnetic resonance imaging or "neuroimaging studies," disease-modifying therapies, biological markers as indicators of drug efficacy, and combination therapies. In addition, the experts speculated as to what will be available in the near future for the improved diagnosis and management of MS. This review summarizes the main points of this discussion and is intended to serve as a reference for neurologists involved in the care of patients with MS.

Adjuvants, Immunologic↗