Assessing Function and Endurance in Adults with Spinal and Bulbar Muscular Atrophy: Validity of the Adult Myopathy Assessment Tool

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA). Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer disease duration (r = -0.29; P \u3c 0.03) and lower serum androgen levels (r = 0.49-0.59; P \u3c 0.001). The AMAT was significantly correlated with strength and functional status (r = 0.82-0.88; P \u3c 0.001). The domains of the AMAT exhibited good internal consistency (Cronbach\u27s α  = 0.77-0.89; P \u3c 0.001). Conclusions. The AMAT is a standardized, performance-based tool that may be used to assess functional limitations and muscle endurance. The AMAT has good internal consistency, and the construct validity of the AMAT is supported by its significant associations with hormonal, strength, and functional characteristics of adults with SBMA. This trial is registered with Clinicaltrials.gov identifier NCT00303446

Intravenous immune globulin in hereditary inclusion body myopathy: a pilot study

BACKGROUND: Hereditary Inclusion Body Myopathy (HIBM) is an autosomal recessive, adult onset, non-inflammatory neuromuscular disorder with no effective treatment. The causative gene, GNE, codes for UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, which catalyzes the first two reactions in the synthesis of sialic acid. Reduced sialylation of muscle glycoproteins, such as α-dystroglycan and neural cell adhesion molecule (NCAM), has been reported in HIBM. METHODS: We treated 4 HIBM patients with intravenous immune globulin (IVIG), in order to provide sialic acid, because IgG contains 8 μmol of sialic acid/g. IVIG was infused as a loading dose of 1 g/kg on two consecutive days followed by 3 doses of 400 mg/kg at weekly intervals. RESULTS: For all four patients, mean quadriceps strength improved from 19.0 kg at baseline to 23.2 kg (+22%) directly after IVIG loading to 25.6 kg (+35%) at the end of the study. Mean shoulder strength improved from 4.1 kg at baseline to 5.9 kg (+44%) directly after IVIG loading to 6.0 kg (+46%) at the end of the study. The composite improvement for 8 other muscle groups was 5% after the initial loading and 19% by the end of the study. Esophageal motility and lingual strength improved in the patients with abnormal barium swallows. Objective measures of functional improvement gave variable results, but the patients experienced improvements in daily activities that they considered clinically significant. Immunohistochemical staining and immunoblotting of muscle biopsies for α-dystroglycan and NCAM did not provide consistent evidence for increased sialylation after IVIG treatment. Side effects were limited to transient headaches and vomiting. CONCLUSION: The mild benefits in muscle strength experienced by HIBM patients after IVIG treatment may be related to the provision of sialic acid supplied by IVIG. Other sources of sialic acid are being explored as treatment options for HIBM

Assessing function and endurance in adults with spinal and bulbar muscular atrophy: validity of the adult myopathy assessment tool.

Purpose. The adult myopathy assessment tool (AMAT) is a performance-based battery comprised of functional and endurance subscales that can be completed in approximately 30 minutes without the use of specialized equipment. The purpose of this study was to determine the construct validity and internal consistency of the AMAT with a sample of adults with spinal and bulbar muscular atrophy (SBMA). Methods. AMAT validity was assessed in 56-male participants with genetically confirmed SBMA (mean age, 53 ± 10 years). The participants completed the AMAT and assessments for disease status, strength, and functional status. Results. Lower AMAT scores were associated with longer disease duration (r = -0.29; P \u3c 0.03) and lower serum androgen levels (r = 0.49-0.59; P \u3c 0.001). The AMAT was significantly correlated with strength and functional status (r = 0.82-0.88; P \u3c 0.001). The domains of the AMAT exhibited good internal consistency (Cronbach\u27s α  = 0.77-0.89; P \u3c 0.001). Conclusions. The AMAT is a standardized, performance-based tool that may be used to assess functional limitations and muscle endurance. The AMAT has good internal consistency, and the construct validity of the AMAT is supported by its significant associations with hormonal, strength, and functional characteristics of adults with SBMA. This trial is registered with Clinicaltrials.gov identifier NCT00303446

A randomized controlled trial of exercise in spinal and bulbar muscular atrophy.

OBJECTIVE: To determine the safety and efficacy of a home-based functional exercise program in spinal and bulbar muscular atrophy (SBMA). METHODS: Subjects were randomly assigned to participate in 12 weeks of either functional exercises (intervention) or a stretching program (control) at the National Institutes of Health in Bethesda, MD. A total of 54 subjects enrolled, and 50 completed the study with 24 in the functional exercise group and 26 in the stretching control group. The primary outcome measure was the Adult Myopathy Assessment Tool (AMAT) total score, and secondary measures included total activity by accelerometry, muscle strength, balance, timed up and go, sit-to-stand test, health-related quality of life, creatine kinase, and insulin-like growth factor-1. RESULTS: Functional exercise was well tolerated but did not lead to significant group differences in the primary outcome measure or any of the secondary measures. The functional exercise did not produce significantly more adverse events than stretching, and was not perceived to be difficult. To determine whether a subset of the subjects may have benefited, we divided them into high and low functioning based on baseline AMAT scores and performed a post hoc subgroup analysis. Low-functioning individuals receiving the intervention increased AMAT functional subscale scores compared to the control group. INTERPRETATION: Although these trial results indicate that functional exercise had no significant effect on total AMAT scores or on mobility, strength, balance, and quality of life, post hoc findings indicate that low-functioning men with SBMA may respond better to functional exercises, and this warrants further investigation with appropriate exercise intensity

Early onset and novel features in a spinal and bulbar muscular atrophy patient with a 68 CAG repeat

AbstractSpinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene. Patients with SBMA have weakness, atrophy, and fasciculations in the bulbar and extremity muscles. Individuals with CAG repeat lengths greater than 62 have not previously been reported. We evaluated a 29year old SBMA patient with 68 CAGs who had unusually early onset and findings not seen in others with the disease. Analysis of the androgen receptor gene confirmed the repeat length of 68 CAGs in both peripheral blood and fibroblasts. Evaluation of muscle and sensory function showed deficits typical of SBMA, and in addition the patient had manifestations of autonomic dysfunction and abnormal sexual development. These findings extend the known phenotype associated with SBMA and shed new insight into the effects of the mutated androgen receptor

Higher D or Li: Probes of Physics beyond the Standard Model

Standard Big Bang Nucleosynthesis at the baryon density determined by the microwave anisotropy spectrum predicts an excess of \li7 compared to observations by a factor of 4-5. In contrast, BBN predictions for D/H are somewhat below (but within ~2 \sigma) of the weighted mean of observationally determined values from quasar absorption systems. Solutions to the \li7 problem which alter the nuclear processes during or subsequent to BBN, often lead to a significant increase in the deuterium abundance consistent with the highest values of D/H seen in absorption systems. Furthermore, the observed D/H abundances show considerable dispersion. Here, we argue that those systems with D/H \simeq 4 \times 10^{-5} may be more representative of the primordial abundance and as a consequence, those systems with lower D/H would necessarily have been subject to local processes of deuterium destruction. This can be accounted for by models of cosmic chemical evolution able to destroy in situ Deuterium due to the fragility of this isotope.Comment: 22 pages, 8 figure

PenQuest Volume 1, Number 2

Table of Contents for this Volume: Untitled by Julie Ambrose Night by Judith Gallo Untitled by Judy Gozdur the shamans by Charles Riddles Untitled by Jerry Connell Untitled by Laura Woods Untitled by LEMA Wicked Bird by Laura Jo Last Untitled by Rick Dentos Untitled by Jeni Moody Untitled by Bettie W. Kwibs Untitled by Joann Stagg The Protector Stood by Laura Jo Last Visions of Salome by Charles Riddles Untitled by Thomas Tutten Kennesaw Line by Don Ova-Dunaway Stone Blood by Mary Ellen C. Wofford Untitled by Roger Whitt Jr. Untitled by C. Wingate Untitled by Doug Dorey Untitled by Karen Blumberg Untitled by Beverly Oviatt Untitled by Virginia Shrader The Crapulous Credo of Charles C. by Charles Riddles the brave and the true by David Reed Untitled by Charles Gutierrez Canoe Creek by Patricia Kraft Untitled by Linda Bobinger The Man in the Iron Lung by Patricia Kraft Untitled by Roger Whitt, Jr. Childish Things by Kathleen Gay Untitled by Joseph Avanzini The Lover by Mary S. Aken Untitled by Ann Harrington And He Taketh Away by David Reed Untitled by Mary Graham Untitled by Melody A. Cummons Untitled by Karen Blumberg To The Poets by Judith Gallo Untitled by Ann Harringto

Clinical features of spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy is an X-linked motor neuron disease caused by a CAG repeat expansion in the androgen receptor gene. To characterize the natural history and define outcome measures for clinical trials, we assessed the clinical history, laboratory findings and muscle strength and function in 57 patients with genetically confirmed disease. We also administered self-assessment questionnaires for activities of daily living, quality of life and erectile function. We found an average delay of over 5 years from onset of weakness to diagnosis. Muscle strength and function correlated directly with serum testosterone levels and inversely with CAG repeat length, age and duration of weakness. Motor unit number estimation was decreased by about half compared to healthy controls. Sensory nerve action potentials were reduced in nearly all subjects. Quantitative muscle assessment and timed 2 min walk may be useful as meaningful indicators of disease status. The direct correlation of testosterone levels with muscle strength indicates that androgens may have a positive effect on muscle function in spinal and bulbar muscular atrophy patients, in addition to the toxic effects described in animal models

Steps toward determination of the size and structure of the broad-line region in active galactic nuclei. 5: Variability of the ultraviolet continuum and emission lines of NGC 3783

We report on the results of intensive ultraviolet spectral monitoring of the Seyfert 1 galaxy NGC 3783. The nucleus of NGC 3783 was observed with the International Ultraviolet Explorer satellite on a regular basis for a total of 7 months, once every 4 days for the first 172 days and once every other day for the final 50 days. Significant variability was observed in both continuum and emission-line fluxes. The light curves for the continuum fluxes exhibited two well-defined local minima or 'dips,' the first lasting is less than or approximately 20 days and the second is less than or approximately 4 days, with additional episodes of relatively rapid flickering of approximately the same amplitude. As in the case of NGC 5548 (the only other Seyfert galaxy that has been the subject of such an intensive, sustained monitoring effort), the largest continuum variations were seen at the shortest wavelengths, so that the continuum became 'harder' when brighter. The variations in the continuum occurred simultaneously at all wavelengths (delta(t) is less than 2 days). Generally, the amplitude of variability of the emission lines was lower than (or comparable to) that of the continuum. Apart from Mg II (which varied little) and N V (which is relatively weak and badly blended with Ly(alpha), the light curves of the emission lines are very similar to the continuum light curves, in each case with a small systematic delay or 'lag.' As for NGC 5548, the highest ionization lines seem to respond with shorter lags than the lower ionization lines. The lags found for NGC 3783 are considerably shorter than those obtained for NGC 5548, with values of (formally) approximately 0 days for He II + O III), and approximately 4 days for Ly(alpha) and C IV. The data further suggest lags of approximately 4 days for Si IV + O IV) and 8-30 days for Si III + C III). Mg II lagged the 1460 A continuum by approximately 9 days, although this result depends on the method of measuring the line flux and may in fact be due to variability of the underlying Fe II lines. Correlation analysis further shows that the power density spectrum contains substantial unresolved power over timescales of is less than or approximately 2 days, and that the character of the continuum variability may change with time