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Biomedical subjects

A E Miller

Publications and source records attributed to A E Miller.

At least 19 recordsLinked to original sources
PubMed2003

Multiple sclerosis characteristics in African American patients in the New York State Multiple Sclerosis Consortium.

The objective of this study was to determine the clinical characteristics of multiple sclerosis (MS) in African American (AA) patients in the New York State Multiple Sclerosis Consortium (NYSMSC) patient registry. The NYSMSC is a group of 18 MS centers throughout New York State organized to prospectively assess clinical characteristics of MS patients. AAs comprise 6% (329) of the total NYSMSC registrants (5602). Demographics, disease course, therapy, and socioeconomic status were compared in AA registrants versus nonAfrican Americans (NAA). There was an increased female preponderance and a significantly younger age at diagnosis in the AA group. AA patients were more likely to have greater disability with increased disease duration. No differences were seen in types of MS and use of disease modifying therapies. Our findings suggest a racial influence in MS. Further genetic studies that consider race differences are warranted to elucidate mechanisms of disease susceptibility.

Adult↗
PubMed2002

Effect of dissolution kinetics on feature size in dip-pen nanolithography.

We have investigated the effects of humidity, tip speed, and dwell time on feature size during dip pen nanolithography. Our results indicate a transition between two distinct deposition regimes occurs at a dwell time independent of humidity. While feature size increases with humidity, the relative increase is independent of dwell time. The results are described by a model that accounts for detachment and reattachment at the tip. The model suggests that, at short dwell times (high speed), the most important parameter controlling the feature size is the activation energy for thiol detachment.

Journal Article↗
PubMed2001

Patient satisfaction after LASIK for myopia.

PURPOSE: To determine satisfaction among patients treated with laser-in-situ-keratomileusis (LASIK) for various degrees of myopia (-0.75 D to -16.00 D) and myopic astigmatism (+0.50 D to +4.50 D) and assess factors which may affect satisfaction. METHODS: One-hundred seventy-four consecutive patients treated with LASIK between November 1, 1997 and October 31, 1998 were surveyed. Charts were reviewed to collect refractive data. RESULTS: Eighty-three patients (163 eyes) returned surveys for a response rate of 53%. Of the responders, 55% were female, the average age was 39.6 years (range 21-59), the mean preoperative sphere was -6.36 +/- 0.23 D, cylinder +0.94 +/- 0.07 D, and spherical equivalent-5.89 +/- 0.23 D. Ninety-six percent of eyes enjoyed freedom from corrective lenses following LASIK. Twenty-nine percent reported reduced night vision clarity following LASIK and 27% noted more eye dryness following LASIK. Overall, 84.8% were at least "very pleased" with the results of the procedure and 97% indicated that they would decide again to have LASIK. Uncorrected visual acuity and lower preoperative cylinder correlated positively with satisfaction, while increased postoperative dry eyes correlated negatively with satisfaction. CONCLUSIONS: This study demonstrates a very high level of patient satisfaction following excimer laser treatment for myopia and myopic astigmatism. A great deal of literature has evaluated objective outcomes of LASIK, but this is one of few studies to examine patient satisfaction.

Adult↗
PubMed2000

Are quantitative functional measures more sensitive to worsening MS than traditional measures?

The authors used data collected prospectively during a multicenter trial in 133 patients with secondary progressive MS to assess the relative sensitivity of quantitative functional tests and traditional measures, including the Expanded Disability Status Scale (EDSS) and Ambulation Index. Quantitative functional measures worsened in 69% of patients during an average of 6 months of observation, whereas the Clinical Global Impression of Change worsened in 33% and the EDSS worsened in 25% of patients. These changes should be interpreted in the context of the test-retest reliability for each measure.

Humans↗
PubMed1999

Development of a multiple sclerosis functional composite as a clinical trial outcome measure.

The primary clinical outcome measure for evaluating multiple sclerosis in clinical trials has been Kurtzke's expanded disability status scale (EDSS). New therapies appear to favourably impact the course of multiple sclerosis and render continued use of placebo control groups more difficult. Consequently, future trials are likely to compare active treatment groups which will most probably require increased sample sizes in order to detect therapeutic efficacy. Because more responsive outcome measures will be needed for active arm comparison studies, the National Multiple Sclerosis Society's Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis appointed a Task Force that was charged with developing improved clinical outcome measures. This Task Force acquired contemporary clinical trial and historical multiple sclerosis data for meta-analyses of primary and secondary outcome assessments to provide a basis for recommending a new outcome measure. A composite measure encompassing the major clinical dimensions of arm, leg and cognitive function was identified and termed the multiple sclerosis functional composite (MSFC). The MSFC consists of three objective quantitative tests of neurological function which are easy to administer. Change in this MSFC over the first year of observation predicted subsequent change in the EDSS, suggesting that the MSFC is more sensitive to change than the EDSS. This paper provides details concerning the development and testing of the MSFC.

Clinical Trials as Topic↗
PubMed1999

A profile of multiple sclerosis: the New York State Multiple Sclerosis Consortium.

We have obtained a current profile of multiple sclerosis York State through a centralized patient registry and standardized data collection instrument associated with the New York State Multiple Sclerosis Consortium of 12 MS centers located throughout the state. Data from the first 3019 patients with clinically definite MS revealed a clear relationship between MS disease type, duration of disease, and severity of physical disability. Patients with relapsing disease had disease durations approximately half as long as those with progressive forms of the disease (means approximately 6 years versus 11 years). The majority of patients with relapsing disease had Expanded Disability Status Scale (EDSS) scores of 4.0 or less (self-sustained, fully ambulatory), whereas the majority of patients with progressive disease types had EDSS scores of 6.0 or greater (at least unilateral assist for walking). These findings emphasize the importance of early intervention in patients with relapsing disease to slow or prevent the accumulation of physical disability associated with progressive types of disease. Progressive disease was associated with lack of full-time employment and being disabled before the age of 60 years. Patients with relapsing disease were more likely to be employed and have private forms of insurance, whereas patients with progressive types of disease were more likely to have government-supported insurance to cover medical expenses.

Adult↗
PubMed1997

Evaluation of recommendations for replication-competent retrovirus testing associated with use of retroviral vectors.

With input from the gene therapy community, CBER is actively examining the recommendations for RCR testing during retroviral vector production, production of ex vivo-transduced cells, and in patients who receive such material. Our initial recommendations were made at a time when our experience with RCR detection assays and clinical use of retroviral vectors was limited. As the gene therapy field has matured, there is an increasing amount of data available on RCR detection assays and from monitoring of patients in clinical trials. The cumulative data give assurance that RCR detection assays in use are of sufficient sensitivity to provide a margin of safety to patients: no patients to date have evidence of RCR infection. However, CBER encourages members of the gene therapy community to continue to submit data to the FDA or to publish data that will enhance the cumulative data base on RCR testing assays, experience with different VPC, and patient monitoring. Based on the analysis of data accumulated to data, and ongoing discussions with members of the gene therapy community, CBER is proposing to discuss changes to the current RCR testing recommendations, as summarized below. RCR testing during production of retroviral vector and ex vivo-transduced cells. Development of characterized standards for RCR testing of supernatant and cells should allow comparison of assay sensitivity. One proposal under consideration is to apply statistical methods to determine how much material needs to be tested independent of the size of the production lot. Data and discussion are still needed to define a limit concentration and a value for probability of detection for RCR testing, while maintaining an appropriate margin of safety. These modifications of RCR testing strategies could lead to improvements in assay sensitivity. Additional discussion and data are also needed to evaluate the current recommendations of the testing for ex vivo-transduced cells: should both cells and supernatant be tested in all cases? RCR testing during patient follow-up. The time points required for RCR testing during patient follow-up need examination. One proposal under consideration is to sample and assay at three time points during the first year of treatment (e.g., 4-6 weeks, 3 months, and 1 year post-treatment). Further discussion is needed to define appropriate additional follow-up. Choice of assays to detect surrogate markers for RCR infection (i.e., serologic or PCR-based assays) should consider mode of vector administration and the patient population. Positive results with such assays should be pursued by direct culture assay to obtain and characterize the infectious viral isolate. These proposals will be the focal point for the discussion at the Retroviral Vector Breakout Session at the 1997 FDA/NIH Gene Therapy Conference. After the 1997 FDA/NIH Gene Therapy Conference, CBR plans to propose revised recommendations for RCR testing for public comment.

Cell Transformation, Viral↗
PubMed1997

A multicenter, randomized, double-blind, placebo-controlled trial of influenza immunization in multiple sclerosis.

We determined the effect of influenza vaccine in patients with relapsing/remitting MS. Considerable controversy surrounds the question of whether to administer influenza vaccines to MS patients. Prevention of a febrile viral illness is clearly desirable in MS, and previous studies suggest that immunization is safe. Despite this, many clinicians avoid vaccination because they fear precipitating an MS exacerbation. We conducted a multicenter, prospective, randomized, double-blind trial of influenza immunization in patients with relapsing/remitting MS. In the autumn of 1993, 104 patients at five MS centers received either standard influenza vaccine or placebo. Patients were followed for 6 months for evaluation of neurologic status and the occurrence of influenza. Influenza was operationally defined as fever > or = 38 degrees C in the presence of coryza, cough, or sore throat at a time when the disease was present in the community. Attacks were defined in the standard manner, requiring objective change in the examination. Patients were examined at 4 weeks and 6 months after inoculation and were contacted by telephone at 1 week and 3 months. They were also examined at times of possible attacks but not when they were sick with flu-like illness. Three vaccine patients and two placebo patients experienced attacks within 28 days of vaccine (no significant difference). Exacerbation rates in the first month for both groups were equal to or less than expected from published series. The two groups showed no difference in attack rate or disease progression over 6 months. Influenza immunization in MS patients is neither associated with an increased exacerbation rate in the postvaccination period nor a change in disease course over the subsequent 6 months.

Double-Blind Method↗
PubMed1997

Characterization of cell cultures derived from Fugu, the Japanese pufferfish.

The Japanese pufferfish (genus Fugu), which possesses a highly compact genome, is becoming a popular model among those interested in sequencing and mapping the genomes of higher vertebrates. Although genomic libraries have been derived and used to study the molecular biology of Fugu, biological material derived from the living organism is difficult to obtain for laboratories distant from the Asian Pacific. We have established cell cultures from two Fugu species: kusafugu, Fugu niphobles, and torafugu, F. rubripes. Cultures derived from F. niphobles fry and F. rubripes eye have been passaged more than 60 times over the course of one year, representing approximately 180 population doublings. Proliferating cultures were also initiated from F. rubripes brain, liver, fin, spleen, kidney, swimbladder, and muscle. Karyotype analyses indicated that F. rubripes eye-derived cells possessed a chromosome number in the diploid range; F. niphobles fry cells were slightly hyperploid. Flow cytometry confirmed that the relative amounts of DNA present in cultured cells from both Fugu species were similar to that measured in blood cells collected from F. rubripes, and approximately one-seventh of that measured in diploid human cells. Telomerase activity was easily detectable in lysates prepared from F. niphobles fry cells and F. rubripes eye cells, consistent with the notion that these cultures are capable of indefinite proliferation.

Animals↗
PubMed1996

Management of patients receiving interferon beta-1b for multiple sclerosis: report of a consensus conference.

Results of a double-blind, placebo-controlled study in ambulatory patients with relapsing-remitting MS showed that interferon beta-1b reduced the rate of exacerbations by one-third compared with placebo and limited new disease activity in the brain as evidenced by MRI. Interferon beta-1b, administered subcutaneously at a dosage of 0.25 mg (8 million IU) every other day is indicated for the treatment of ambulatory patients with relapsing-remitting MS. Interferon beta-1b may help a wider range of patients, but it should be prescribed only for patients with a diagnosis of clinically definite or laboratory-supported definite MS. The decision to treat a patient with interferon beta-1b should be individualized; that is, based on each patient's clinical presentation and course of MS. The most common adverse effects include (1) injection-site reactions and (2) flu-like symptoms, which are generally manageable and usually abate after the first few months of treatment. Spasticity may increase. Patients with severe depression or suicidal ideation should be monitored carefully, and symptomatic treatment should be pursued. Interferon beta-1b is contraindicated in pregnant and nursing women. Interferon beta-1b is effective in reducing the progression of total disease burden as seen on MRI in patients with MS. Its use is relatively straightforward and generally does not require alteration in the symptomatic treatment of MS. Patient education and support remain the mainstays of maintaining compliance through the early phases of therapy.

Female↗
PubMed1993

Gender differences in strength and muscle fiber characteristics.

Strength and muscle characteristics were examined in biceps brachii and vastus lateralis of eight men and eight women. Measurements included motor unit number, size and activation and voluntary strength of the elbow flexors and knee extensors. Fiber areas and type were determined from needle biopsies and muscle areas by computerized tomographical scanning. The women were approximately 52% and 66% as strong as the men in the upper and lower body respectively. The men were also stronger relative to lean body mass. A significant correlation was found between strength and muscle cross-sectional area (CSA; P < or = 0.05). The women had 45, 41, 30 and 25% smaller muscle CSAs for the biceps brachii, total elbow flexors, vastus lateralis and total knee extensors respectively. The men had significantly larger type I fiber areas (4597 vs 3483 microns2) and mean fiber areas (6632 vs 3963 microns2) than the women in biceps brachii and significantly larger type II fiber areas (7700 vs 4040 microns2) and mean fiber areas (7070 vs 4290 microns2) in vastus lateralis. No significant gender difference was found in the strength to CSA ratio for elbow flexion or knee extension, in biceps fiber number (180,620 in men vs 156,872 in women), muscle area to fiber area ratio in the vastus lateralis 451,468 vs 465,007) or any motor unit characteristics. Data suggest that the greater strength of the men was due primarily to larger fibers. The greater gender difference in upper body strength can probably be attributed to the fact that women tend to have a lower proportion of their lean tissue distributed in the upper body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Presence of cross-reactive antibodies to HTLV-1 and absence of antigens in patients with multiple sclerosis.

Antibodies to HTLV-1, as determined by ELISA, were highly elevated in the serum samples of four out of four (100%) patients with TSP, moderately elevated in four out of four (100%) HTLV-1 carriers, slightly elevated in 12 out of 34 (35%) patients with MS, and absent from the serum samples of 34 normal subjects. Western blot analysis showed that the antibodies to HTLV-1 antigens in MS serum were heterogeneous. Cultivation of peripheral blood lymphocytes (PBLs) from patients with MS or normal subjects did not generate HTLV-1 core p19 antigen in the supernatant of culture medium, whereas cultivation of PBLs from patients with TSP and carriers of HTLV-1 generated core p19 antigen after 3 days for up to 28 days of cultivation. HTLV-1 antigens were also expressed on the surface of PBLs in three out of four patients with TSP and in two out of four HTLV-1 carriers on days 14 and 28 of cultivation, as measured by indirect immunofluorescence or alkaline phosphatase staining, but were not found in PBLs of any of 34 patients with MS or 34 normal subjects. The data indicate that although cross-reacting antibodies appear in the serum of some patients with MS, not enough evidence exists to suggest that HTLV-1 antigen is being produced in MS or that HTLV-1 plays a role in the pathogenesis of this disease.

Adult↗
PubMed1992

Activation of immunoglobulin control elements in transgenic mice.

To assess the role interleukins and mitogens play in regulating immunoglobulin (Ig) gene expression via the Ig enhancer and promoter, transgenic mice carrying two different Ig gene regulatory regions were generated. One, EmukCAT, contains the Ig heavy chain enhancer (Emu) and the kappa light chain promoter driving the chloramphenicol acetyltransferase (CAT) gene. In the other, delta EmukCAT, CAT is under the control of the kappa promoter alone. Emu and kappa relative activity were assessed by CAT assay. In EmukCAT mice, low CAT expression was consistently found in spleen, bone marrow, mesenteric lymph node, and thymus but not in brain, lung, or kidney. In delta EmukCAT mice, CAT expression was detectable just above background in lymphoid tissues, suggesting a basic level of tissue specificity in the absence of the enhancer. Whole spleen cell cultures prepared from the mice were treated with lymphokines and mitogens. Lipopolysaccharide (LPS), concanavilin A (Con A), interleukin 6 (IL-6), and interferon-gamma (IFN-gamma) increased CAT expression to varying extents in cells derived from EmukCAT mice but not in spleen cells prepared from delta EmukCAT mice. Thus, the presence of Emu, in addition to the kappa promoter, is essential for the stimulation of CAT expression mediated by these factors. B cells from EmukCAT mice were separated by density into populations of small and large cells. In untreated small B cells, no CAT expression was detected and only addition of LPS resulted in an increase in CAT expression. In large B cells, CAT was expressed at a low level without addition of exogenous factors. Incubation with LPS, IL-6, Con A and IFN-gamma caused CAT expression to increase several-fold. This transgenic system provides a means to identify exogenous factors that activate Ig enhancers and promoters.

Animals↗