NMR‐based approach to the analysis of radiopharmaceuticals: radiochemical purity,specific activity,and radioactive concentration values by proton and tritium NMR spectroscopy

Compounds containing tritium are widely used across the drug discovery and development landscape. These materials are widely utilized because they can be efficiently synthesized and produced at high specific activity. Results from internally calibrated ³H and ¹H nuclear magnetic resonance (NMR) spectroscopy suggests that at least in some cases, this calibrated approach could supplement or potentially replace radio‐high‐performance liquid chromatography for radiochemical purity, dilution and scintillation counting for the measurement of radioactivity per volume, and liquid chromatography/mass spectrometry analysis for the determination of specific activity. In summary, the NMR‐derived values agreed with those from the standard approaches to within 1% to 9% for solution count and specific activity. Additionally, the NMR‐derived values for radiochemical purity deviated by less than 5%. A benefit of this method is that these values may be calculated at the same time that ³H NMR analysis provides the location and distribution of tritium atoms within the molecule. Presented and discussed here is the application of this method, advantages and disadvantages of the approach, and a rationale for utilizing internally calibrated ¹H and ³H NMR spectroscopy for specific activity, radioactive concentration, and radiochemical purity whenever acquiring ³H NMR for tritium location.     

Mechanisms of the contextual interference effect in individuals poststroke

Although intermixing different motor learning tasks via random schedules enhances long-term retention compared with "blocked" schedules, the mechanism underlying this contextual interference effect has been unclear. Furthermore, previous studies have reported inconclusive results in individuals poststroke. We instructed participants to learn to produce three grip force patterns in either random or blocked schedules and measured the contextual interference effect by long-term forgetting: the change in performance between immediate and 24-h posttests. Nondisabled participants exhibited the contextual interference effect: no forgetting in the random condition but forgetting in the blocked condition. Participants at least 3 mo poststroke exhibited no forgetting in the random condition but marginal forgetting in the blocked condition. However, in participants poststroke, the integrity of visuospatial working memory modulated long-term retention after blocked schedule training: participants with poor visuospatial working memory exhibited little forgetting at 24 h. These counterintuitive results were predicted by a computational model of motor memory that contains a common fast process and multiple slow processes, which are competitively updated by motor errors. In blocked schedules, the fast process quickly improved performance, therefore reducing error-driven update of the slow processes and thus poor long-term retention. In random schedules, interferences in the fast process led to slower change in performance, therefore increasing error-driven update of slow processes and thus good long-term retention. Increased forgetting rates in the fast process, as would be expected in individuals with visuospatial working memory deficits, led to small updates of the fast process during blocked schedules and thus better long-term retention.     

Hemispheric specialization in the co-ordination of arm and trunk movements during pointing in patients with unilateral brain damage

During pointing movements involving trunk displacement, healthy subjects perform stereotypically, selecting a strategy in which the movement is initiated with either the hand or trunk, and where the trunk continues after the end of the hand movement. In a previous study, such temporal co-ordination was not found in patients with left-hemispheric brain lesions reaching with either their dominant paretic or with their non-dominant non-paretic arm. This co-ordination deficit may be associated in part with the presence of a lesion in the dominant left hemisphere. If so, then no deficit should be observed in patients with stroke-related damage in their non-dominant right hemisphere moving with their ipsilesional arm. To verify this, 21 right-hand dominant adults (7 who had had a stroke in the right hemisphere, 7 who had had a stroke in the left hemisphere and 7 healthy subjects) pointed to two targets located on a table in front of them in the ipsilateral and contralateral workspace. Pointing was done under three movement conditions: while not moving the trunk, while bending the trunk forward and while bending the trunk backwards. The experiment was repeated with the non-paretic arm of patients with stroke and for the right and left arms of healthy subjects. Kinematic data were recorded (Optotrak). Results showed that, compared to healthy subjects, arm-trunk timing was disrupted in patients with stroke for some conditions. As in patients with lesions in the dominant hemisphere, arm-trunk timing in those with lesions in the non-dominant hemisphere was equally more variable than movements in healthy subjects. However, patients with dominant hemisphere lesions used significantly less trunk displacement than those with non-dominant hemisphere lesions to accomplish the task. The deficit in trunk displacement was not due to problems of trunk control or sitting balance since, in control experiments, all subjects were able to move the trunk the required distance, with and without the added weight of the limb. Results support the hypothesis that the temporal co-ordination of trunk and arm recruitment during pointing movements is mediated bilaterally by each hemisphere. However, the difference in the range of trunk displacement between patients with left and right brain lesions suggests that the left (dominant) hemisphere plays a greater role than the right in the control of movements involving complex co-ordination between the arm and trunk. Electronic Publication     

Health care decision making in southern county

We combine two standard approaches to analyze power and influence in health policy formulation within a moderately large county in the south. Intrinsic methodologic weaknesses are discussed and several conclusions are drawn regarding power in the health care sector of that community. The most significant finding is the shift in power over time, away from the individuals to committees and health care organizations. The ignorance of most physicians about the broader health care issues that affect the community was reflected in their lack of recognition by others in the community as influential decision makers. The insular relationship of the university to the rest of the community was also noted. Past racial politics had a continuing effect on later health policy formulation. These findings are discussed in light of current and past issues. Because we had promised confidentiality to the persons we interviewed, fictitious names were given to the county, the institutions, and the interviewees.     

The EXCITE trial: attributes of the Wolf Motor Function Test in patients with subacute stroke

The Wolf Motor Function Test (WMFT) has been used in rehabilitation studies of chronic stroke patients, but until now its psychometric properties have not been evaluated in patients with subacute stroke. Two hundred twenty-nine participants with subacute stroke (3-9 months postinjury) at 7 research sites met inclusion criteria for the EXCITE Trial and were randomized into immediate or delayed (by 1 year) constraint-induced movement therapy treatment. All evaluations were undertaken by assessors standardized in the administration of the WMFT and masked to treatment designation. Participants were also assessed using the Fugl Meyer Motor Assessment (FMA). Delayed group members had measurements repeated 2 weeks following baseline assessment to determine learning or exposure effects. The results demonstrate that the WMFT differentiated higher from lower functioning participants across sites; scores were uninfluenced by hand dominance or affected side. Women exhibited slower performance times than men. The Functional Ability scale (FAS) portion of the WMFT also revealed lower scores among lower functioning participants and women. Minimal changes were observed after repeating the WMFT among delayed group participants 2 weeks later. The FMA revealed similar results when the total group was divided into higher and lower functional levels at its midpoint score of 33. The WMFT discriminates higher from lower functioning participants tested across research sites. Comparable findings using the FMA support the criterion validity of the WMFT.     

Sensory cueing effects on maximal speed gait initiation in persons with Parkinson's disease and healthy elders

Researchers have suggested that sensory cues can improve gait initiation in persons with Parkinson's disease (PD); however, there is little research that documents the effects of sensory cues on gait initiation. The purpose of this study was to examine the effects of auditory and cutaneous sensory cues on maximal speed gait initiation in person's with PD and healthy elderly. Seven persons with PD of moderate severity (mean AGE=69 years) and seven age, gender, and height matched healthy elders participated. Temporal, kinematic and center of pressure (COP) data were recorded as participants performed eight trials within four randomly ordered conditions (no cue (NC), a single auditory cue (SA), repetitive auditory cues (RA), and repetitive cutaneous cues (RC)). In each condition, participants were instructed to perform each gait initiation trial at their maximal speed. In all conditions, person's with PD reacted more slowly and moved less far than did the matched elders. Relative to conditions with NCs, sensory cueing resulted in decreased double limb support (DLS), and increased COP displacement and velocity in both groups. However, in both groups, displacements and velocities of the swing limb and sacrum during the sensory-cued conditions were less than those during the NC condition. These results suggest that when movement speed is a primary goal, sensory cues may interfere with swing limb and body movement outcomes during the gait initiation task in both person's with PD and healthy elders.     

Methods for a multisite randomized trial to investigate the effect of constraint-induced movement therapy in improving upper extremity function among adults recovering from a cerebrovascular stroke

This article describes the study design, methodological considerations, and demographic characteristics of a phase III RCT to determine if 1) constraint-induced therapy (CI therapy) can be applied with therapeutic success 3 to 9 months after stroke across different sites, 2) gains that might occur persist over 2 years, 3) initial level of motor ability determines responsiveness to CI therapy, and 4) the treatment effect differs between those treated before 9 months and after 1 year. Six sites will screen and recruit poststroke survivors stratified on initial level of motor ability and after randomization allocate participants to immediate or delayed intervention. Primary outcomes include a laboratory-based measure of function (Wolf Motor Function Test [WMFT]) and a real-world participant-centered functional use measure (Motor Activity Log [MAI]). Secondary outcomes concern function, behavior, and compliance. This is the first multisite, single-blind RCT of a formal training intervention for upper extremity rehabilitation in subacute stroke in the United States.     

Safety, tolerability and immunogenicity of VAQTA given concomitantly versus nonconcomitantly with other pediatric vaccines in healthy 12-month-old children

BACKGROUND: The objective of this study is to assess whether hepatitis A vaccine is immunogenic and well tolerated when administered to 12-month-old children alone or concomitantly with other routinely administered pediatric vaccines. METHODS: Six hundred seventeen healthy 12-month-old children were randomized to receive dose 1 of hepatitis A vaccine given alone or concomitantly with measles-mumps-rubella vaccine and varicella vaccine and dose 2 of hepatitis A vaccine given alone or concomitantly with diphtheria-tetanus-acellular pertussis vaccine and optionally with oral or inactivated poliovirus vaccine. Participants were followed for clinical adverse experiences and serologic responses to all vaccine antigens. Antibody responses were compared with historical controls for some indices. RESULTS: The safety profile was generally comparable whether hepatitis A vaccine was administered alone or concomitantly with other vaccines. When administered alone, the hepatitis A seropositivity rate was 98.3% and 100% for dose 1 and dose 2, respectively, and after dose 2 was similar to historical rates and the geometric mean titers were similar between initially seropositive and initially seronegative subjects (6207 and 6810 mIU/mL, respectively). After concomitant administration with hepatitis A vaccine, antibody responses to measles, mumps, rubella, diphtheria, tetanus and filamentous hemagglutinin (98.8%, 99.6%, 100%, 98.6%, 100% and 83.3%, respectively) were similar to historical controls and response to poliovirus was demonstrated, but immune responses to varicella zoster virus (79%) and pertussis toxoid (76%) were inferior to historical controls. CONCLUSIONS: Hepatitis A vaccine is highly immunogenic and generally well tolerated when administered to healthy children as young as 12 months of age regardless of initial hepatitis A serostatus and can be administered concomitantly with measles-mumps-rubella vaccine and oral or inactivated poliovirus vaccine.