A randomized placebo-controlled pilot study of the efficacy and safety of D-cycloserine in people with chronic back pain.

BACKGROUND: Few effective pharmacological treatment options exist for chronic back pain, the leading cause of disability in the US, and all are associated with significant adverse effects. OBJECTIVE: To determine the efficacy and safety of D-cycloserine, a partial agonist to the N-methyl-D-aspartate receptor, in the treatment of chronic low back pain. METHODS: A total of 41 participants with chronic back pain who met all inclusion and exclusion criteria were enrolled in a double-blind, placebo-controlled randomized pilot trial of D-cycloserine. Treatment was administered orally for six weeks at escalating daily doses of 100 mg, 200 mg, and 400 mg, each for two weeks. The primary outcome measure was back pain intensity using the Numeric Rating Scale (0-10). Secondary measures were back pain-related questionnaires: McGill Pain Questionnaire short form, painDETECT, PANAS, and BDI. The pre-specified analysis was a two-way repeated measures analysis of variance. RESULTS: A treatment difference was observed between groups treated with D-cycloserine and placebo at six weeks of 1.05 ± 3.1 units on the Numeric Rating Scale, with an effect size of 0.4 and p = 0.14. This trend of better chronic back pain relief with D-cycloserine was also observed in the secondary measures. No safety issues were seen. CONCLUSION: The difference in mean pain between the D-cycloserine and placebo groups did not reach statistical significance. However, a clinically meaningful effect size in the magnitude of pain relief was observed with a consistent pattern across multiple outcome measures with good safety, supporting further research into the effectiveness of D-cycloserine for chronic back pain

Protein coding assignment of the S genes of the avian reovirus S1133

The protein coding assignments for each of the S genes of the avian reovirus S1133 have been determined. In vitro translation of RNA derived from individual S dsRNA genome segments demonstrated that the largest S gene, S1, codes for the smallest protein, [sigma]c; the [sigma]A for [sigma]A; the S3 gene for [sigma]C and the S4 gene for [sigma]NS. No other gene products could be identified. By examination of appropriate reassortant viruses, these assignments were confirmed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25764/1/0000325.pd

Clinical and biochemical characteristics of autoantibody systems in polymyositis and dermatomyositis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26177/1/0000256.pd

Pathogenesis and differential diagnosis of the swan-neck deformity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25068/1/0000499.pd

A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis

The effects of an analgesic treatment (lidocaine patches) on brain activity in chronic low back pain (CBP) and in knee osteoarthritis (OA) were investigated using serial fMRI (contrasting fMRI between before and after two weeks of treatment). Prior to treatment brain activity was distinct between the two groups: CBP spontaneous pain was associated mainly with activity in medial prefrontal cortex, while OA painful mechanical knee stimulation was associated with bilateral activity in the thalamus, secondary somatosensory, insular, and cingulate cortices, and unilateral activity in the putamen and amygdala. After 5% lidocaine patches were applied to the painful body part for two weeks, CBP patients exhibited a significant decrease in clinical pain measures, while in OA clinical questionnaire based outcomes showed no treatment effect but stimulus evoked pain showed a borderline decrease. The lidocaine treatment resulted in significantly decreased brain activity in both patient groups with distinct brain regions responding in each group, and sub-regions within these areas were correlated with pain ratings specifically for each group (medial prefrontal cortex in CBP and thalamus in OA). We conclude that the two chronic pain conditions involve distinct brain regions, with OA pain engaging many brain regions commonly observed in acute pain. Moreover, lidocaine patch treatment modulates distinct brain circuitry in each condition, yet in OA we observe divergent results with fMRI and with questionnaire based instruments

Brain Morphological Signatures for Chronic Pain

Chronic pain can be understood not only as an altered functional state, but also as a consequence of neuronal plasticity. Here we use in vivo structural MRI to compare global, local, and architectural changes in gray matter properties in patients suffering from chronic back pain (CBP), complex regional pain syndrome (CRPS) and knee osteoarthritis (OA), relative to healthy controls. We find that different chronic pain types exhibit unique anatomical ‘brain signatures’. Only the CBP group showed altered whole-brain gray matter volume, while regional gray matter density was distinct for each group. Voxel-wise comparison of gray matter density showed that the impact on the extent of chronicity of pain was localized to a common set of regions across all conditions. When gray matter density was examined for large regions approximating Brodmann areas, it exhibited unique large-scale distributed networks for each group. We derived a barcode, summarized by a single index of within-subject co-variation of gray matter density, which enabled classification of individual brains to their conditions with high accuracy. This index also enabled calculating time constants and asymptotic amplitudes for an exponential increase in brain re-organization with pain chronicity, and showed that brain reorganization with pain chronicity was 6 times slower and twice as large in CBP in comparison to CRPS. The results show an exuberance of brain anatomical reorganization peculiar to each condition and as such reflecting the unique maladaptive physiology of different types of chronic pain

In vitro characterization of an avian reovirus vaccine strain

In vitro studies were performed to characterize the vaccine strain, designated P100, derived from the arthrogenic reovirus isolate, S1133, by vold adaptation. P100 appeared to be temperature sensitive, shown by a marked drop in titer and efficiency of plaquing after incubation at 41[deg]. Studies indicated that genomic double-stranded RNA and protein synthesis were severely restricted at the elevated temperature. Differences in the growth behavior of P100 and S1133 at 37[deg] were also noted. The vaccine strain seemed to be more cell associated than S1133. Three outer coat proteins of P100 grown at 37[deg] displayed mobilities different from those of S1133 by PAGE. It is possible that alterations in these proteins may have some relationship to the growth characteristics observed for the P100 strain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25241/1/0000683.pd

QCD strings with spinning quarks

We construct a consistent action for a massive spinning quark on the end of a QCD string that leads to pure Thomas precession of the quark's spin. The string action is modified by the addition of Grassmann degrees of freedom to the string such that the equations of motion for the quark spin follow from boundary conditions, just as do those for the quark's position.Comment: REVTeX4, 10 pages, no figure

A Murine Model of Polymyositis Induced by Coxsackievirus B1 (Tucson Strain)

A murine model of polymyositis induced by coxsackievirus B1, Tucson strain (CVB T ) is described. Intraperitoneal CVB T inoculation of CD 1 Swiss mice less than 48 hours old resulted in proximal hindquarter weakness that was first apparent 7 days after viral challenge and persisted for more than 10 weeks. Electromyographic and histologic evidence of a continuing myositis was present during this entire period of time. However, virus was not detectable later than 2 weeks post infection, despite clinical progression of disease. The finding of electromyographic and histologic abnormalities in CVB T -infected mice, long after virus had cleared and neutralizing antibody production evoked, suggests that persistent myositis may be immunologically mediated, triggered by the initial acute viral infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37767/1/1780270411_ftp.pd

Critique of a Pion Exchange Model for Interquark Forces

I describe four serious defects of a widely discussed pion exchange model for interquark forces: it doesn't solve the "spin-orbit problem" as advertised, it fails to describe the internal structure of baryon resonances, it leads to disastrous conclusions when extended to mesons, and it is not reasonably connected to the physics of heavy-light systems.Comment: 20 pages, 6 figures; some clarifications and references adde