Additional therapy promotes a continued pattern of improvement in upper-limb function and independence post-stroke.

BACKGROUND: Upper-limb motor impairment after stroke is common and disabling. Growing evidence suggests that rehabilitation is effective in the chronic period. However, there is limited knowledge on the effects of ongoing targeted rehabilitation programs on patient outcomes. OBJECTIVES: This study investigated the effects of delivering two programs of dose-matched evidence-based upper-limb rehabilitation to community-dwelling post-acute stroke patients with low, moderate and high motor-function. MATERIALS AND METHODS: 12 patients (2 female) aged 50.5±18.2 years and 13.8±10.8 months post-stroke completed 2-weeks of modified-Constraint-Induced Movement Therapy followed by 2-weeks of Wii-based Movement Therapy after a mean interval of 9.6±1.1 months (range 6-19months). Function was assessed at 6 time points (i.e. before and after each therapy program and 6-month follow-up after each program). Primary outcome measures were the Wolf Motor Function Test timed-tasks (WMFT-tt), upper-limb Fugl-Meyer Assessment (F-M) and the Motor Activity Log Quality of Movement Scale (MALQOM). Improvement and maintenance was analyzed using Paired T-Tests and Wilcoxon Signed Rank Tests. RESULTS: Upper-limb function significantly improved on all primary outcome measures with the first therapy program (WMFT-tt p=0.008, F-M p=0.007 and MALQOM p<0.0001). All scores continued to improve with the second therapy program with significant improvements in the F-M (p=0.048) and the MALQOM (p=0.001). CONCLUSIONS: All patients showed a pattern of continued improvement in upper-limb motor-function and independence in activities of daily living. These improvements demonstrate the benefit of ongoing post-stroke rehabilitation for community-dwelling stroke survivors for individuals of varying baseline functional status.

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions.

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54-75%) and specificity of 47% (41-53%); SEPSIS-3 criteria had a sensitivity of 86% (76-92%) and specificity of 32% (27-38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5-5.6) and 1.6 (1.3-2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63-0.76)), followed by NEWS (0.58 (0.51-0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49-0.61)) and quickSOFA score (0.56 (0.49-0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction.

Visual phenomena induced by relativistic carbon ions with and without Cerenkov radiation.

Exposing the human eye to individual carbon ions (6C+) moving at relativistic speeds results in visual phenomena that include point flashes, streaks, and larger diffuse flashes. The diffuse flashes have previously been observed by astronauts in space but not in laboratory experiments with particles of high atomic number and energy. They are observed only when the nucleus moves fast enough to generate Cerenkov radiation.

Visual sensations induced by Cerenkov radiation.

Pulses of relativistic singly charged particles entering the eyeball induce a variety of visual phenomena by means of Cerenkov radiation generated during their passage through the vitreous. These phenomena are similar in appearance to many of the visual sensations experienced by Apollo astronauts exposed to the cosmic rays in deep space.

Light flashes observed on skylab 4: the role of nuclear stars.

The astronauts on Skylab 4 observed bursts of intense visual light flash activity when their spacecraft passed through the South Atlantic Anomaly. Flash rates as high as 20 per minute have in the past been considered unexpectedly high. When the effect of nuclear interactions in and near the retina is included, the apparent anomaly is removed.

Visual sensations induced by relativistic nitrogen nuclei.

The ability of the human eye to detect nitrogen nuclei that enter the retina at speeds just above the Cerenkov threshold has been confirmed in an experiment at the Princeton Particle Accelerator. A system for beam transport and subject alignment delivered individual nitrogen nuclei onto a spot 3 millimeters in diameter on the retina at a visual angle of 7 degrees on the temporal side of the fovea. The beam particles entered the retina within 25 degrees of normal and induced visual sensations that had the appearance of streaks for three out of four subjects.

Acceleration of argon ions to 1.17x1010 electron volts.

Argon ions were accelerated to 1.17x10(10) electron volts in the Princeton Particle Accelerator. The synchrotron was tuned by use of a neon beam with a charge-to-mass ratio equal to that of the argon ions. The fully accelerated argon ions were detected by the observation of etched tracks in cellulose nitrate sheets and also by the use of scintillation counters. Predictions of the range and of the characteristics of argon tracks in plastics were confirmed.

Selective activation of human finger muscles after stroke or amputation.

Individuated finger movements of the human hand require selective activation of particular sets of muscles. Such selective activation is controlled primarily by the motor cortex via the corticospinal tract. Is this selectivity therefore lost when lesions damage the corticospinal tract? Or when the motor cortex reorganizes after amputation? We studied finger movements in normal human subjects and in patients who had recovered substantially from pure motor hemiparesis caused by lacunar strokes, which damage the corticospinal tract without affecting other pathways. Even after substantial recovery from these strokes, individuation of finger movements remained reduced-both for flexion/extension and for adduction/ abduction motion of the fingers. Stroke subjects regained the ability to move the instructed digit through a normal range, but unintentional motion of other digits was increased. This increase did not result from a change in the passive biomechanical coupling of the fingers. Rather, voluntary contractions of muscles that move the intended digit were accompanied by inappropriate contractions in muscles acting on additional digits. These observations suggest that the normal corticospinal system produces individuated finger movements not only by selectively activating certain muscles, but also by suppressing activation of other muscles during voluntary effort to move a given digit. In a separate experiment, reversible amputation of the hand was produced in normal subjects by ischemic nerve block at the wrist. Motor output to the intrinsic muscles and sensory input both become blocked under these conditions, effectively amputating the hand from the nervous system. But the long extrinsic muscles that flex and extend the digits remain normally innervated, and thus flexion forces still can be generated at the fingertips. During reversible amputation of the hand produced by ischemic nerve block, the ability of subjects to activate subdivisions of extrinsic muscles and to exert flexion force at individual fingertips continued to show essentially normal selectivity. Voluntary activation of the remaining muscles thus continues to be selective after amputation, in spite of both the loss of sensory input from the amputated hand, and reorganization within the primary motor cortex. During cortical reorganization after amputation, then, voluntary patterns of motor output intended for finger muscles may not be lost. We therefore examined activity in the stump muscles of above-elbow amputees, who have no remaining hand muscles. Different movements of the phantom hand were accompanied by different patterns of EMG in remaining proximal muscles, distinct from the EMG patterns associated with movement of the phantom elbow. We infer that voluntary motor output patterns that normally control finger movements after amputation may become diverted to remaining proximal muscles.

Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.

The regulation of protein metabolism in the human heart has not previously been studied. In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state. We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations. Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged. These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.

Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia.

Myocardial regions perfused through a coronary stenosis may cease contracting, but remain viable. Clinical observations suggest that increased glucose utilization may be an adaptive mechanism in such "hibernating" regions. In this study, we used a combination of 13C-NMR spectroscopy, GC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-13C]glucose during a 3-4-h period of acute ischemic hibernation. During low-flow ischemia [3-13C]alanine enrichment was higher, relative to plasma [1-13C]glucose enrichment, in ischemic than in nonischemic regions of the heart, suggesting a greater contribution of exogenous glucose to glycolytic flux in the ischemic region (approximately 72 vs. approximately 28%, P < 0.01). Both the fraction of glycogen synthase present in the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rate of incorporation of circulating glucose into glycogen (94 +/- 25 vs. 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady state [4-13C)glutamate/[3-13C]alanine enrichment ratios demonstrated that glucose-derived pyruvate supported 26-36% of total tricarboxylic acid cycle flux in all regions, however, indicating no preference for glucose over fat as an oxidative substrate in the ischemic myocardium. Thus during sustained regional low-flow ischemia in vivo, the ischemic myocardium increases its utilization of exogenous glucose as a substrate. Upregulation is restricted to cytosolic utilization pathways, however (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.

Changes in measures of motor axon excitability with age.

OBJECTIVE: Threshold tracking is a novel technique that permits examination of the excitability of human axons in vivo. Protocols have been validated for sensory and motor axons, but there are limited data on the changes in the excitability of motor axons with age. This study aimed to determine such changes from the third to the eighth decades. METHODS: Sixty healthy subjects aged 22-79, 10 per decade, were studied using the TRONDXM4 protocol of the QTRAC threshold-tracking program to assess motor axon function. The median nerve was stimulated at the wrist and the compound muscle action potential was recorded from the thenar muscles. RESULTS: There was an increase in threshold in elderly subjects, associated with a decrease in slope of the stimulus-response curves. Strength-duration time constant and threshold electrotonus to depolarising and hyperpolarising currents of up to 40% did not change significantly with aging. The current-threshold relationship was similar across all decades for subthreshold depolarising currents, but the slope of the current-threshold relationship was significantly steeper the older the subjects for hyperpolarising currents, particularly those greater than 40% of threshold. There was also a significant decrease in supernormality in the recovery cycle with increasing age. CONCLUSIONS: The threshold of axons increases with age and the extent of supernormality decreases. There may also be greater inward rectification in motor axons, perhaps due to greater activity of I(H), the hyperpolarisation-activated conductance, though this is only significant with hyperpolarising currents greater than 40% of the threshold current. SIGNIFICANCE: Many indices of axonal excitability, such as strength-duration time constant, the relative refractory period, late subnormality, threshold electrotonus and the depolarising side of the current-threshold relationship, do not change significantly with age. For other indices, age-related changes may be due to a combination of non-neural factors that alter current access to the node of Ranvier, changes in the axon and its myelination and, possibly, changes in channel activity and/or changes in extracellular [K(+)](o).

Single-ion dosemeter based on floating gate memories.

Floating Gate (FG) nonvolatile memories are based on a tiny polysilicon layer (the FG) which can be permanently charged with electrons or holes, thus changing the threshold voltage of a MOSFET. Every time a FG is hit by a high energy ion, it experiences a charge loss, depending on the ion linear energy transfer (LET) and on the transistor geometrical and electrical characteristics. This paper discusses the opportunities to use this devices as single an ion dosemeter with sub-micrometer spatial resolution and capable of distinguish the impinging ion LET.

Sensitivity and dynamic range of FGMOS dosemeters.

UVPROM memory devices employing FGMOS transistors as memory cells make excellent dosemeters for applications involving ionising radiation. With proper preparation and programming, these devices can be used in remote-sensing applications in high-radiation environments with no power required during exposure.

Effect of non-insulin-dependent diabetes mellitus on myocardial insulin responsiveness in patients with ischemic heart disease.

BACKGROUND: Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit poor clinical outcomes from myocardial ischemia. This may reflect an impairment in their cardiac insulin-response system. METHODS AND RESULTS: We used AV balance and intracoronary infusion techniques to compare the intrinsic cardiac responsiveness to insulin in 26 coronary disease patients with (n=13) and without (n=13) NIDDM. During fasting, NIDDM hearts demonstrated lower fractional extraction of glucose from arterial plasma than controls (1.0+/-0.5% versus 2.1+/-0.5%, P<0.05) despite higher circulating insulin levels (26+/-5 versus 13+/-4 microU. mL, P<0.05). This was compensated for by higher circulating glucose levels, so that net cardiac glucose uptake in the 2 groups was equivalent (5.2+/-1.1 versus 5.3+/-1.1 micromol. min). Intracoronary insulin infusion produced an approximately 3-fold increase in fractional extraction and net uptake of glucose across the heart in both groups (to 3.7+/-0.4% and 18.3+/-3.5 micromol. min in NIDDM and to 5.4+/-0.7% and 17.7+/-4.3 micromol. min in controls) accompanied by an approximately 30% increase in net lactate uptake, suggesting preserved insulin action on both glucose uptake and glucose oxidation in the NIDDM heart. In nondiabetics, insulin consistently increased coronary blood flow, but this effect was absent in NIDDM. CONCLUSIONS: In contrast to their peripheral tissues and coronary vasculature, the myocardium of patients with NIDDM expresses a competent insulin-response system with respect to glucose metabolism. This suggests that insulin resistance is mediated at the level of individual organs and that different mechanisms are involved in muscle and vascular tissue.

Persistent changes in myocardial glucose metabolism in vivo during reperfusion of a limited-duration coronary occlusion.

BACKGROUND: Rapid reperfusion of an occluded coronary artery salvages regional mechanical function, but this benefit may not be realized for hours or days because of postischemic stunning. Recovery from stunning is incompletely understood but may involve adaptive changes in heart glucose metabolism. METHODS AND RESULTS: To examine whether reversible coronary occlusion produces sustained changes in regional glucose metabolism in vivo, we performed a 20-minute left coronary artery occlusion followed by 24 hours of open-artery reperfusion in intact rats. Coronary occlusion produced stunning of the anterolateral left ventricle that resolved over 24 hours. When examined at 24 hours, reperfused regions were fully contractile and viable by vital staining and microscopy but demonstrated 25% reduction in blood flow and 50% increased uptake of circulating glucose, as estimated by in vivo [(13)N]NH(3) and [(18)F]fluorodeoxyglucose (FDG) tracer uptake. Reperfused regions had largely inactive glycogen synthase, low rates of glycogen synthesis, and persistent 50% glycogen depletion but increased flux of plasma [1-(13)C]glucose into myocardial [3-(13)C]alanine, indicating preferential shunting of imported glucose away from storage and into glycolysis. CONCLUSIONS: Sustained increases in regional glycolytic consumption of circulating glucose occur during reperfusion of a limited-duration coronary occlusion. This suggests a role for glycolytic ATP in the recovery from postischemic stunning in vivo. Furthermore, [(13)N]NH(3) /FDG regional mismatch may constitute a clinically accessible late metabolic signature of regional myocardial ischemia.

Precise positioning of patients for radiation therapy.

We have developed a number of immobilization schemes which permit precise daily positioning of patients for radiation therapy. Pretreatment and post-treatment radiographs have been taken with the patient in the treatment position and analyzed to determine the amount of intratreatment movement. Studies of patients in the supine, seated and decubitus positions indicate mean movements of less than 1 mm with a standard deviation of less than 1mm. Patients immobilized in the seated position with a bite block and a mask have a mean movement of about 0.5 mm +/- 0.3 mm (s.d.), and patients immobilized in the supine position with their necks hyperextended for submental therapy evidence a mean movement of about 1.4 mm +/- 0.9 mm (s.d.). With the exception of those used for the decubitus position, the immobilization devices are simply fabricated out of thermoplastic casting materials readily available from orthopedic supply houses. A study of day-to-day reproducibility of patient position using laser alignment and pretreatment radiographs for final verification of position indicates that the initial laser alignment can be used to position a patient within 2.2 mm +/- 1.4 mm (s.d.) of the intended position. These results indicate that rigid immobilization devices can improve the precision of radiotherapy, which would be advantageous with respect to both tumor and normal tissue coverage in certain situations.

Radiation therapy of retroperitoneal soft tissue sarcomas.

Between 1971 and 1982, 23 patients have been treated with radiation therapy at the Massachusetts General Hospital (MGH) for retroperitoneal soft tissue sarcomas. Seventeen patients were treated with curative intent and six with palliative intent. Of the patients treated with curative intent, the 5 year actuarial survival rate was 54% and the 5 year actuarial local control rate was also 54%. With a complete surgical resection local tumor control was obtained in 5 of 7 patients (71%), 4 of 7 (57%) with incomplete resection and 1/3 (33%) with no resection having local control. The radiation dose appeared to influence tumor control with 2 of 6 patients (33%) having local control with less than 5,000 cGy compared to 0 of 5 patients with doses of 5,000 to 6,000 cGy and 5 of 6 (83%) with doses greater than 6,000 cGy. An effect of tumor grade on either local control or on rate of metastasis formation could not be demonstrated in this series. Long-term local control and survival appears to be associated with maximal surgical resection and high dose radiation therapy.

Conservative treatment of uveal melanoma: probability of eye retention after proton treatment.

Enucleation was performed after proton treatment in 57 of 1006 (5.7%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986. Only 2% of 99 patients with small tumors and 4% of 566 patients with intermediate size tumors underwent enucleation after treatment; 10% of 341 patients with large tumors lost the treated eye. No eyes were removed after 52 months, with 89% of enucleations performed during the first 36 months after treatment. Eye retention rates at 60 months were 89.1 +/- 3.0% for the entire group, and 97 +/- 3.7%, 92.7 +/- 3.1%, and 78.3 +/- 7.0% in patients with small, intermediate, and large tumors, respectively. Significantly greater enucleation rates were observed in patients with large tumors than in those with intermediate tumors (p = less than .0001), in patients with tumor height greater than 8 mm relative to those with tumors less than or equal to 8 mm, p = (less than .0001), with tumor diameter greater than 16 mm compared to less than or equal to 16 mm, (p = less than .0001), and with tumor involvement of the ciliary body compared to involvement of the choroid only (p = less than .0001). Possible strategies to decrease the likelihood of enucleation in patients at apparently increased risk of losing the eye after conservative therapy, that is, those with large tumors involving the ciliary body, might include a lower total dose, a more protracted treatment course, or a lower radiation dose and adjuvant treatment with chemotherapy and/or immunotherapy, with hyperthermia, or with other radiation sensitizers.

Light scattering and fluorescence by small particles having internal structure.

We consider two related, yet distinct queries: 1. How does the internal morphology of a small particle affect the elastic light scattering signals? We have devised an algorithm, presently accurate for particles comparable only to small biological spheres (diameter less than 1 micron), which suggests that light scattering is sensitive to internal morphology only in the backward directions. Accordingly, observations should be obtained in these directions when probing for internal morphology. 2. How are fluorescent signals affected when the active molecules are variously distributed within small particles? One cannot assume that the fluorescent signals are simply proportional to the number of active molecules contained in the particle because there may also be a dependence upon the geometrical and optical properties of the particle and upon the particular spatial distribution of these molecules within the particle. Indeed, even the measured emission spectrum may be affected by such morphological features. Here, too, these calculations are mainly restricted to small particles (diameter less than 1 micron) in which the fluorescent molecules are isotropic and immobile. Under these conditions the effects are quite dramatic. These effects should be considered in quantitative procedures which utilize fluorescence for determining the concentration of specific molecules in small particles such as biological cells. They may provide a clue for discriminating among cells which differ morphologically or in which the spatial distribution of the fluorescent moiety differs. These effects may be minimized by utilizing a light source which is polarized perpendicularly to the scattering plane.

Effect of hyperinsulinemia on myocardial fluorine-18-FDG uptake.

UNLABELLED: This study was performed to evaluate the effect of insulin on myocardial kinetics of 18F-fluorodeoxyglucose (FDG) and glucose in patients with ischemic heart disease. METHODS: Twelve male patients (age range 54-79 yr; mean age 69 +/- 8 yr) were studied during the fasting awake state. Patients with diabetes and previous myocardial infarction of the left anterior descending vascular bed were excluded from the study. Patients were injected with a 185-MBq (5-mCi) bolus of FDG during arterial and coronary sinus catheterization. Thirty minutes after FDG injection, paired basal arterial and coronary sinus blood samples were taken for the measurement of FDG and glucose uptake. Thereafter, a primed (100 mU x m(-2) x min(-1) for 10 min) continuous (50 mU x m(-2) x min(-1) infusion of insulin was administered for 60 min using the euglycemic clamp technique, and blood samples were repeated. Blood samples also were taken periodically for the measurement of arterial free fatty acids and insulin. RESULTS: Euglycemic insulin infusion lowered arterial concentrations of free fatty acids, reducing myocardial extraction of free fatty acids by 85% and stimulated uptake of glucose and FDG. Myocardial glucose and FDG extraction fractions (%) increased from 1 +/- 1 and 2 +/- 2 at baseline to 8 +/- 2 and 10 +/- 3 during insulin infusion, respectively. The lumped constant value was estimated to be 1.44 +/- 0.14 (r = 0.87) for the fasted state, 0.99 +/- 0.07 (r = 0.74) during insulin infusion and 1.00 +/- 0.05 (r = 0.92) when both groups of data were pooled together. CONCLUSION: The data obtained in this study show that FDG uptake quantitatively traces glucose uptake during physiological hyperinsulinemia in patients with ischemic heart disease.