Longitudinal Persistence of Meningeal Enhancement on Postcontrast 7T 3D-FLAIR MRI in Multiple Sclerosis.

BACKGROUND AND PURPOSE: Preliminary research has demonstrated that postgadolinium 3D-FLAIR MR imaging at 7T may be a valuable tool for detecting abnormal meningeal enhancement and inflammation in MS; however, researchers have not systematically investigated its longitudinal persistence. We hypothesized that persistence of meningeal enhancement in MS varies on the basis of pattern of enhancement as well as demographic and clinical factors such as treatment status, disease phenotype, and disability score. MATERIALS AND METHODS: Thirty-one subjects with MS were prospectively scanned before and after intravenous contrast administration at 2 time points, approximately 1 year apart. Fifteen subjects in the cohort were scanned at another time approximately 1 year later. Foci of enhancement were categorized into 4 subtypes: subarachnoid spread/fill, subarachnoid nodular, vessel wall, and dural foci. We reviewed follow-up scans to determine whether foci changed between time points and then compared persistence with demographic and clinical variables. RESULTS: Persistence ranged from 71% to 100% at 1 year and 73% to 100% at 2 years, depending on the enhancement pattern. Subarachnoid spread/fill and subarachnoid nodular subtypes persisted less often than vessel wall and dural foci. Persistence was not significantly different between those on/off treatment and those with progressive/nonprogressive disease phenotypes. The number of persisting foci was significantly different in subjects with/without increasing Expanded Disability Status Scale scores (median, 12 versus 7.5, P = .04). CONCLUSIONS: Longitudinal persistence of meningeal enhancement on 3D-FLAIR at 7T in MS varies by pattern of enhancement and correlates with worsening disability; however, it is not significantly different in those on/off treatment or in those with progressive/nonprogressive disease phenotypes.

Lesion Heterogeneity on High-Field Susceptibility MRI Is Associated with Multiple Sclerosis Severity.

BACKGROUND AND PURPOSE: Susceptibility MR imaging contrast variations reflect alterations in brain iron and myelin content, making this imaging tool relevant to studies of multiple sclerosis lesion heterogeneity. In this study, we aimed to characterize the relationship of high-field, susceptibility contrasts in multiple sclerosis lesions to clinical outcomes. MATERIALS AND METHODS: Twenty-four subjects with multiple sclerosis underwent 7T MR imaging of the brain, disability examinations, and a fatigue inventory. The inverse of T2* relaxation time (R2*), frequency, and relative susceptibility (from quantitative susceptibility mapping) were analyzed in 306 white matter lesions. RESULTS: Most lesions were hypointense on R2* (88% without a rim, 5% with). Lesions that were hyperintense on quantitative susceptibility mapping were more frequent in relapsing-remitting than in progressive multiple sclerosis (54% versus 35%, P = .018). Hyperintense lesion rims on quantitative susceptibility maps were more common in progressive multiple sclerosis and patients with higher levels of disability and fatigue. Mean lesion R2* was inversely related to disability and fatigue and significantly reduced in progressive multiple sclerosis. Relative susceptibility was lower in lesions in progressive multiple sclerosis (median, -0.018 ppm; range, -0.070 to 0.022) than in relapsing-remitting MS (median, -0.010 ppm; range, -0.062 to 0.052; P = .003). CONCLUSIONS: A progressive clinical phenotype and greater disability and fatigue were associated with lower R2* and relative susceptibility values (suggestive of low iron due to oligodendrocyte loss) and rimmed lesions (suggestive of chronic inflammation) in this multiple sclerosis cohort. Lesion heterogeneity on susceptibility MR imaging may help explain disability in multiple sclerosis and provide a window into the processes of demyelination, oligodendrocyte loss, and chronic lesion inflammation.

Longitudinal changes in diffusion tensor-based quantitative MRI in multiple sclerosis.

OBJECTIVE: To estimate longitudinal changes in a quantitative whole-brain and tract-specific MRI study of multiple sclerosis (MS), with the intent of assessing the feasibility of this approach in clinical trials. METHODS: A total of 78 individuals with MS underwent a median of 3 scans over 2 years. Diffusion tensor imaging indices, magnetization transfer ratio, and T2 relaxation time were analyzed in supratentorial brain, corpus callosum, optic radiations, and corticospinal tracts by atlas-based tractography. Linear mixed-effect models estimated annualized rates of change for each index, and sample size estimates for potential clinical trials were determined. RESULTS: There were significant changes over time in fractional anisotropy and perpendicular diffusivity in the supratentorial brain and corpus callosum, mean diffusivity in the supratentorial brain, and magnetization transfer ratio in all areas studied. Changes were most rapid in the corpus callosum, where fractional anisotropy decreased 1.7% per year, perpendicular diffusivity increased 1.2% per year, and magnetization transfer ratio decreased 0.9% per year. The T2 relaxation time changed more rapidly than diffusion tensor imaging indices and magnetization transfer ratio but had higher within-participant variability. Magnetization transfer ratio in the corpus callosum and supratentorial brain declined at an accelerated rate in progressive MS relative to relapsing-remitting MS. Power analysis yielded reasonable sample sizes (on the order of 40 participants per arm or fewer) for 1- or 2-year trials. CONCLUSIONS: Longitudinal changes in whole-brain and tract-specific diffusion tensor imaging indices and magnetization transfer ratio can be reliably quantified, suggesting that small clinical trials using these outcome measures are feasible.

MRI of the corpus callosum in multiple sclerosis: association with disability.

Inflammatory demyelination and axon damage in the corpus callosum are prominent features of multiple sclerosis (MS) and may partially account for impaired performance on complex tasks. The objective of this article was to characterize quantitative callosal MRI abnormalities and their association with disability. In 69 participants with MS and 29 healthy volunteers, lesional and extralesional callosal MRI indices were estimated via diffusion tensor tractography. expanded disability status scale (EDSS) and MS functional composite (MSFC) scores were recorded in 53 of the participants with MS. All tested callosal MRI indices were diffusely abnormal in MS. EDSS score was correlated only with age (r = 0.51). Scores on the overall MSFC and its paced serial auditory addition test (PASAT) and 9-hole peg test components were correlated with callosal fractional anisotropy (r = 0.27, 0.35, and 0.31, respectively) and perpendicular diffusivity (r = -0.29, -0.30, and -0.31) but not with overall callosal volume or callosal lesion volume; the PASAT score was more weakly correlated with callosal magnetization-transfer ratio (r = 0.21). Anterior callosal abnormalities were associated with impaired PASAT performance and posterior abnormalities with slow performance on the 9-hole peg test. In conclusion, abnormalities in the corpus callosum can be assessed with quantitative MRI and are associated with cognitive and complex upper-extremity dysfunction in MS.

Localization and environmental regulation of MCP-like proteins in Rhodobacter sphaeroides.

Chemotaxis to many compounds by Rhodobacter sphaeroides requires transport and at least partial metabolism of the chemoeffector. Previous investigations using phototrophically grown cells have failed to find any homologues of the MCP chemoreceptors identified in Escherichia coli. However, using an antibody raised against the highly conserved domain of E. coli Tsr, MCP-like proteins were identified in R. sphaeroides WS8N. Analysis using Western blotting and immunogold electron microscopy showed that expression of these MCP-like proteins is environmentally regulated and that receptors are targeted to two different cellular locations: the poles of the cells and the cytoplasm. In aerobically grown cells, these proteins were shown by immunoelectron microscopy to localize predominantly to the cell poles and to an electron-dense body in the cytoplasm. Western blot analysis indicated a 17-fold reduction in protein concentration when cells were grown in the light. The number of immunogold particles was also dramatically reduced in anaerobically light-grown cells and their cellular distribution was altered. Fewer receptors localized to the cell poles and more particles randomly distributed within the cell, but the cytoplasmic cluster remained. These trends were more pronounced in cells grown anaerobically under dim light than in those grown anaerobically under bright light, suggesting that expression is controlled by redox state and either light intensity or the extent of photosynthetic membrane synthesis. Recent work on E. coli chemosensing suggests that oligomerization of receptors and chemosensory proteins is important for sensory signalling. The data presented here suggest that this oligomerization can occur with cytoplasmic receptors and also provides an explanation for the multiple copies of chemosensory proteins in R. sphaeroides.

Identification of a methyl-accepting chemotaxis protein in Rhodobacter sphaeroides.

Analysis of the DNA sequence directly upstream of the chemotaxis operon of Rhodobacter sphaeroides identified a single gene whose product has strong similarity to the methyl-accepting chemotaxis proteins (MCPs) found in enteric bacteria. The deduced protein had a highly conserved signalling sequence and only one very hydrophobic region at the N-terminus, in contrast to enteric MCPs. A possible cytoplasmic location of the majority of the protein was supported by Western blotting. The mcpA gene was insertionally inactivated and the resulting phenotype examined using swarm plate assays. The mutant lacking McpA lost chemotaxis to a wide range of attractant stimuli but only under aerobic conditions; it retained almost normal chemotaxis under anaerobic/photosynthetic conditions. The identification of a sensory protein which is active only under one set of growth conditions suggests that R. sphaeroides probably has several MCPs, which co-ordinately respond to changes in environmental conditions. Southern hybridization at relaxed stringency to the conserved sequence of the R. sphaeroides and Caulobacter crescentus mcp genes identified three possible additional mcp genes.

The effect of pH on the growth and motility of Rhodobacter sphaeroides WS8 and the nature of the driving force of the flagellar motor.

Rhodobacter sphaeroides WS8 grew, and swam vigorously, over the pH range 6 to 9. Sustained motility was, however, observed in populations of cells resuspended at pH values between 4.9 and 10.4, although the mean run speed was reduced at the extremes of pH. The ability of R. sphaeroides to swim in strong alkaline conditions prompted the question of whether motility at alkaline pH was powered by a sodium motive force, as has been found in the facultative alkalophilic Bacillus and Vibrio species, particularly as motility was found to be sensitive to the sodium channel inhibitor amiloride. The nature of the driving force of the flagellar motor was therefore investigated. It was found that R. sphaeroides was motile over the same pH range in the absence and presence of sodium ions. The protonophore CCCP was found to inhibit motility under all conditions, whereas monensin, an inhibitor of sodium pumps, had no effect upon motility in the presence or absence of sodium. It was concluded that the delta p is the driving force for the flagellar motor in R. sphaeroides at all values of pH. Amiloride, a specific inhibitor of the sodium-driven flagellar motor in alkalophilic Bacillus and Vibrio was shown to act non-specifically on the proton driven motor of R. sphaeroides, reducing the swimming speed of this organism in media with and without sodium to the same extent and over the complete pH range. Measurement of the delta p by using the electrochromic absorbance change of the carotenoid pigments to measure delta psi and 31P-NMR to measure delta pH showed that the maximum delta p was about -215 mV. At pH 10 the cells swam more slowly and the delta p was about -90 mV. These data suggest that the flagellar motor of R. sphaeroides is proton-driven under all conditions with a threshold for motor rotation below -90 mV and saturation at above -90 mV and below -215 mV.

Swimming speed and chemokinetic response of Rhodobacter sphaeroides investigated by natural manipulation of the membrane potential.

The delta psi of R. sphaeroides, grown under high light to reduce the levels of light-harvesting bacteriochlorophyll, was naturally manipulated using light intensity. The relationship between delta psi and the swimming speed of free swimming populations of cells was investigated. After de-energisation by incubation in the dark there was an apparent threshold of about -13 mV which had to be overcome before functional motor rotation could resume and at -45 mV the motor saturated. Further increases in delta psi over -45 mV did not increase the free swimming velocity. However, when a chemokinetic effector was added there was an increase in swimming speed, even though the delta psi was well above saturation, indicating that the chemokinetic response is independent of normal relationship between motor rotation and delta psi.

An evaluation of morphine and oxymorphone administered via patient-controlled analgesia (PCA) or PCA plus basal infusion in postcesarean-delivery patients.

The analgesic efficacy and adverse effects of morphine and oxymorphone in 32 patients who received traditional patient-controlled analgesia (PCA) following cesarean delivery were compared with those in 32 other patients receiving the same agents via PCA plus basal opioid infusion (PCA + BI). All patients were operated upon during epidural anesthesia with 2% lidocaine and 1:200,000 epinephrine to achieve a T4 sensory level. Upon first complaint of pain in the recovery room, patients were given a titrated iv loading dose of the assigned opioid until comfortable and were then provided with a programmable PCA device. Group I (PCA) consisted of two subsets in which incremental boluses of morphine (1.8 mg, n = 16) or oxymorphone (0.3 mg, n = 16) could be self-administered via conventional PCA. Patients in group II (PCA + BI) received a basal infusion of morphine (0.6 mg/hour, n = 16) or oxymorphone (0.1 mg/hour, n = 16) in addition to self-administered boluses of 1.8 and 0.3 mg, respectively. Patients were evaluated for 24 h following initiation of analgesic therapy, and 10-cm visual analog scales (VAS) were utilized at selected intervals to assess pain at rest, pain during movement, and satisfaction with therapy. The level of sedation and incidence of nausea/vomiting and pruritus were also recorded. Patients utilizing PCA + BI noted significant reductions in resting pain scores with oxymorphone and decreased pain during movement with both opioids when compared with individuals using PCA alone (P less than 0.05). There were no significant differences between treatment groups in 24-h dose requirements or patient satisfaction with therapy (P = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison of morphine, meperidine, and oxymorphone as utilized in patient-controlled analgesia following cesarean delivery.

Seventy-five patients (n = 75) undergoing elective cesarean delivery during epidural anesthesia were randomly assigned to receive one of three opioid analgesics via patient-controlled analgesia (PCA) when they first complained of pain in the recovery room. Following administration of an analgesic loading dose, patients were allowed to self-administer morphine 1.8 mg, meperidine 18 mg, or oxymorphone 0.3 mg iv every 8 min as required. Data collected during the 24-h observation period included visual analog scale (VAS) pain scores at rest and during movement, VAS patient satisfaction scores, total drug administered, the ratio of attempts/injections, and the incidence of nausea/vomiting, sedation, and pruritus. After adjusting for narcotic potency, no differences in 24-h dose requirements were noted between treatment groups (NS). All patients achieved an excellent level of analgesia at rest (NS); however, onset was most rapid with oxymorphone (P less than 0.05). The percentage of patients reporting severe pain during movement was highest in the meperidine group (P less than 0.05). Oxymorphone was associated with the highest incidence of nausea and vomiting (P less than 0.05), whereas increased sedation and pruritus were noted with morphine. Patient satisfaction with drug effect demonstrated significant negative correlations with resting pain scores and degree of sedation. Whereas morphine is a more commonly utilized PCA analgesic, the excellent analgesia, low incidence of sedation, and high patient satisfaction provided by meperidine and oxymorphone suggested useful alternatives.

A comparison of oxymorphone and fentanyl as narcotic supplements in general anesthesia.

The safety and efficacy of two potent opiate analgesics, fentanyl and oxymorphone, used as adjuncts in general anesthesia, were studied in 39 patients undergoing elective gynecologic surgery of at least 2 hours duration. Based on a potency ratio of 10:1, patients received either fentanyl 6.5 micrograms/kg or oxymorphone 65 micrograms/kg prior to a thiopental 2 to 3 mg/kg succinylcholine induction and endotracheal intubation. Additional maintenance narcotic and isoflurane were administered as required by the "blinded" anesthesiologist in response to hemodynamic alterations 15% above a presurgical baseline. Overall analysis included hemodynamic response at preset intraoperative intervals, total anesthetic requirements, and stability of vital signs in the recovery room. Blood pressure and heart rate were reliably controlled with either agent; however, less narcotic (ml) and recovery room analgesics were required in the oxymorphone-treated group (p less than 0.05). Decreased naloxone requirements (p less than 0.05) and a more rapid emergence suggested that fentanyl was a safer agent when administered in relatively unrestricted fashion.