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PubMed1996

Analytical Solutions and Simulations for Spin-Echo Measurements of Diffusion of Spins in a Sphere with Surface and Bulk Relaxation

Nuclear spins (in molecules) are considered to be diffusing in a sphere in a linearly inhomogeneous magnetic field (field gradient) that is imposed during a spin-echo NMR experiment. Relaxation of magnetization both in the bulk medium and on the inner surface of the sphere is assumed to occur. Analytical solutions were obtained for the relevant modified diffusion (partial differential) equation by using separation of variables with a Green's function (propagator) and three different boundary conditions. Neuman [J. Chem. Phys. 60, 4508 (1974)] analyzed the same physical system, but with no relaxation, to obtain an expression that relates the NMR spin-echo signal intensity to the magnitude of the magnetic field gradient, the spin-echo time, and the intrinsic molecular diffusion coefficient. The present analysis was based on that originally used by Neuman and, like the latter, it employed the assumption of a Gaussian distribution of phases of the spin magnetizations. This assumption, while rendering a tractable solution, nevertheless limits its range of applicability; this aspect, and the convergence properties of the series solutions were investigated in conjunction with numerical simulations made with diffusion modeled as a three-dimensional random (Monte Carlo) walk. A novel prediction for spheres with finite surface relaxation and a given radius is the presence of two minima in a graph of the normalized spin-echo signal intensity versus the reciprocal of the diffusion coefficient.

Journal Article↗
PubMed2006

Walking through protein sequence space.

Following the original idea of Maynard Smith on evolution of the protein sequence space, a novel tool is developed that allows the "space walk", from one sequence to its likely evolutionary relative and further on. At a given threshold of identity between consecutive steps, the walks of many steps are possible. The sequences at the ends of the walks may substantially differ from one another. In a sequence space of randomized (shuffled) sequences the walks are very short. The approach opens new perspectives for protein evolutionary studies and sequence annotation.

ATP-Binding Cassette Transporters↗
PubMedDate not supplied

A cheA cheW operon in Borrelia burgdorferi, the agent of Lyme disease.

Borrelia burgdorferi sensu stricto homologues of cheA and cheW were cloned and characterized. A combination of strategies such as polymerase chain reaction (PCR) using degenerate primers, random-primed gene walking PCR and construction of a lamda library were used to identify the putative cheA gene. Sequence analysis of the DNA fragments obtained from the CT strain identified a 2,592-bp open reading frame (ORF) encoding an 864-amino-acid protein with significant similarity (53-64.6% identical residues) to the CheA of several genera of eubacteria. In particular, hallmarks of a histidine kinase family were found such as the location of the histidine autophosphorylation domain very close to the NH2 terminus and the nucleotide-binding site. A second ORF located immediately downstream from the putative borrelial cheA gene encoded a 195-amino-acid protein which displayed a high level of similarity to bacterial CheW. Using reverse transcription PCR, we demonstrated that cheA and cheW form an operon with an upstream, unidentified ORF. The cheA and cheW homologues were located at 722-737 kbp, 738-768 kbp and 743-824 kbp on the linear chromosomes of B. burgdorferi sensu stricto, B. garinii and B. afzelii, respectively. Identification of cheA and cheW is the first step toward elucidation of a possible role of chemotaxis in virulence of the Lyme disease borreliae.

Amino Acid Sequence↗
PubMed2003

Influence of executive function on locomotor function: divided attention increases gait variability in Alzheimer's disease.

OBJECTIVES: To evaluate how cognitive function and divided attention affect gait in Alzheimer's disease (AD). DESIGN: Cross-sectional intervention study with subjects serving as their own controls. SETTING: Inpatient unit and outpatient clinic for patients with dementia located at a Veterans Affairs Medical Center. PARTICIPANTS: Twenty-eight patients diagnosed with probable AD. INTERVENTION: Performance of a cognitive task (repeating random digits) while walking. MEASUREMENTS: Neuropsychological measures including clock drawing, verbal fluency, and digit span were obtained along with the Clinical Dementia Rating and Mini-Mental State Examination, the measures of dementia severity. Gait speed and stride-to-stride variability of gait rhythm were measured, once during normal walking and once during dual-task walking. RESULTS: During usual walking, subjects walked slowly and with greater gait variability than older adults without AD. Gait speed was significantly reduced (P<.012) and gait variability increased with dual-task walking (P<.007). The effect on gait variability was larger than the effect on gait speed (P<.015). Executive and neuropsychological function were significantly (P<.02) associated with the increased gait variability that occurred when walking with divided attention but not with gait speed or usual, single-task walking measures of gait. CONCLUSION: Divided attention markedly impairs the ability of patients with AD to regulate the stride-to-stride variations in gait timing. This susceptibility to distraction and its effect on stride time variability, a measure of gait unsteadiness, could partially explain the predilection to falling observed in patients with dementia. The results also support the concept that persons with AD have significant impairments in the cognitive domain of attention and that locomotor function relies upon cognitive, especially executive, function.

Aged↗
PubMed2004

EMG analysis of peroneal and tibialis anterior muscle activity prior to foot contact during functional activities.

The purpose of this investigation was to determine the pre-activity of the tibialis anterior (TA), peroneus longus (PL), and peroneus brevis (PB) prior to foot contact during three conditions. Twenty-six subjects (age 22 +/- 2 yrs; 15 male, 11 female) with no lower extremity injuries reported for data collection. Data were collected from each subject's dominant leg using surface electromyography (EMG). EMG electrodes were applied over the test muscles using a standard protocol. A heel-toe strike transducer was affixed to the bottom of the subject's shoe. The subject completed two randomized trials of walking on a treadmill (5.6 kph), jogging on a treadmill (9.3 kph) and drop landing from a 38 cm box. Isometric reference positions (IRPs) were recorded for the TA, PL, and PB. Muscle data were normalized to IRPs and the average processed EMG for the 200 ms prior to heel strike during walking and jogging and prior to toe strike when dropping from the box was used for analysis. A one-way repeated measures MANOVA was used to detect differences in pre-activity of the muscles between the three conditions. Univariate tests were used to determine differences for each muscle and Tukey's was applied post hoc to determine individual effect differences. The MANOVA revealed significant differences among the three conditions (F2.50 = 10.770; P < .0005). Average TA activity was significantly higher during jogging (Tukey's; P < .0005). Significant differences existed between each condition for the TA. Average PL and PB activity was significantly higher when drop landing (Tukey's; P < .0005). There was no significant difference between walking and jogging for the PL and PB. The amount of muscle pre-activity occurring before heel or toe strike provides useful information for the examination of reaction times to unexpected inversion during dynamic activities.

Adult↗
PubMed1993

The descriptive epidemiology of selected physical activities and body weight among adults trying to lose weight: the Behavioral Risk Factor Surveillance System survey, 1989.

Few population-based studies have described the physical activity patterns of individuals trying to lose weight. We analysed cross-sectional, self-reported data from 6125 men and 12,557 women (> or = 18 years of age) from 40 states who reported in the 1989 Behavioral Risk Factor Surveillance System (BRFSS) survey that they were trying to lose weight. The BRFSS is a state-based telephone survey of non-institutionalized US adults, which utilizes a multi-stage cluster design based on the Waksberg method of random digit dialing. Walking was the most prevalent physical activity (48%), followed by aerobics (8%), gardening (5%), cycling (5%), and running (4%); however, activity choices varied by socio-demographic characteristics. Among both sexes, the prevalence of overweight (BMI > or = 30 kg/m2) decreased significantly with increasing level of activity (P < or = 0.001). Regression results showed that among both sexes and in most age groups, those who ran or jogged, performed aerobics, or cycled weighed less (P < or = 0.001) than those who reported no activity--independent of height, race, education, smoking, and caloric restriction. Walking was also associated with lower weight (P < or = 0.001) among persons aged 40 or older. Because walking is highly prevalent among persons in most socio-demographic strata and is accessible and low risk, its relative merits should be stressed in developing interventions for weight loss and maintenance.

Adult↗
PubMed2002

Effect of glutathione infusion on leg arterial circulation, cutaneous microcirculation, and pain-free walking distance in patients with peripheral obstructive arterial disease: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the effects of glutathione on pain-free walking distance (PFWD) and hemodynamic parameters in patients with peripheral artery disease. PATIENTS AND METHODS: Forty patients with Fontaine stage II peripheral artery disease who were seen between September 2000 and March 2001 at the vascular laboratory and ward of the Division of Vascular Medicine and Rehabilitation at Verona University were studied in a double-blind, placebo-controlled trial. The patients were randomly assigned (20 per group) to treatment with intravenous glutathione twice a day or saline solution twice a day for 5 days. Treatments were administered in a double-blind manner. The 2 groups of patients underwent measurement of PFWD by strain-gauge plethysmography and laser Doppler flowmetry (with postischemic test) of the symptomatic leg at rest and after treadmill test. All measurements and tests were repeated 12 hours after the last infusion. RESULTS: Between the 2 groups, hemodynamic tests showed no differences in baseline values and at rest after treatment. At rest, no differences were observed between basal and posttreatment values; findings in the saline group were similar during tests before and after the infusion period. In the glutathione group, we observed increases in PFWD (196+/-15 vs 143+/-11 m; P<.04), macrocirculatory flow after treadmill test with plethysmography at the end of treatment (9.3+/-2 vs 2.8+/-0.5 mL per 100 mL/min; P<.002), and postischemic hyperemia with laser Doppler flowmetry, registered as perfusion units (PU), at the end of infusions (14.4+/-3.2 vs 6.18+/-1.5 PU; P<.005), with a greater area under the curve after treatment (705+/-103 vs 508+/-45 PU/s; P<.001) and reduced time to flow motion (32+/-4 vs 48+/-11 seconds; P<.05). CONCLUSION: In patients with peripheral artery disease, glutathione prolongs PFWD and shows an improvement of macrocirculatory and microcirculatory parameters.

Aged↗
PubMed2000

"On" freezing in Parkinson's disease: resistance to visual cue walking devices.

OBJECTIVE: To measure "on" freezing during unassisted walking (UW) and test if two devices, a modified inverted stick (MIS) and a visual laser beam stick (LBS) improved walking speed and number of "on" freezing episodes in patients with Parkinson's disease (PD). BACKGROUND: Multiple visual cues can overcome "off' freezing episodes and can be useful in improving gait function in parkinsonian patients. These devices have not been specifically tested in "on" freezing, which is unresponsive to pharmacologic manipulations. METHODS: Patients with PD, motor fluctuations and freezing while "on," attempted walking on a 60-ft track with each of three walking conditions in a randomized order: UW, MIS, and LBS. Total time to complete a trial, number of freezes, and the ratio of walking time to the number of freezes were compared using Friedman's test. RESULTS: Twenty-eight patients with PD, mean age 67.81 years (standard deviation [SD] 7.54), mean disease duration 13.04 years (SD 7.49), and mean motor Unified Parkinson's Disease Rating Scale score "on" 32.59 (SD 10.93), participated in the study. There was a statistically significant correlation of time needed to complete a trial and number of freezes for all three conditions (Spearman correlations: UW 0.973, LBS 0.0.930, and MIS 0.842). The median number of freezes, median time to walk in each condition, and median walking time per freeze were not significantly different in pairwise comparisons of the three conditions (Friedman's test). Of the 28 subjects, six showed improvement with the MIS and six with the LBS in at least one outcome measure. CONCLUSION: Assisting devices, specifically based on visual cues, are not consistently beneficial in overcoming "on" freezing in most patients with PD. Because this is an otherwise untreatable clinical problem and because occasional subjects do respond, cautious trials of such devices under the supervision of a health professional should be conducted to identify those patients who might benefit from their long-term use.

Aged↗
PubMed1996

Comparison of the efficacy of a demand oxygen delivery system with continuous low flow oxygen in subjects with stable COPD and severe oxygen desaturation on walking.

BACKGROUND: Provision of ambulatory oxygen using an intermittent pulsed flow regulated by a demand oxygen delivery system (DODS) greatly increases the limited supply time of standard portable gaseous cylinders. The efficacy of such a system has not previously been studied during submaximal exercise in subjects with severe chronic obstructive pulmonary disease (COPD) in whom desaturation is likely to be great and where usage is often most appropriate. METHODS: Fifteen subjects with severe COPD and oxygen desaturation underwent six minute walk tests performed in random order to compare the efficacy of a demand oxygen delivery system (DODS) with continuous flow oxygen. Walk distance, breathlessness, oxygen saturation, resting time, and recovery time (objective and subjective) were recorded and compared for each walk. RESULTS: Breathing continuous oxygen compared with baseline air breathing improved mean walk distance (295 m versus 271 m) and recovery time (47 seconds versus 112 seconds), whilst the lowest recorded saturation (81% versus 74%) and time desaturated below 90% (201 seconds versus 299 seconds) were reduced. When the DODS was compared with air breathing only the walk distance changed (283 m versus 271 m). A comparison of the DODS with continuous oxygen breathing showed the DODS to be less effective at oxygenating subjects with inferior lowest saturation (78% versus 81%), time spent below 90% (284 seconds versus 201 seconds), time to objective recovery (83 seconds versus 47 seconds), and walk distance (283 m versus 295 m). CONCLUSIONS: Neither of the delivery systems was able to prevent desaturation in these subjects. The use of continuous flow oxygen, however, was accompanied by improvements in oxygenation, walk distance, and recovery time compared with air breathing. The DODS produced only a small increase in walk distance without elevation of oxygen saturation, but was inferior to continuous flow oxygen in most of the measured variables when compared directly.

Administration, Inhalation↗
PubMed1996

Gait problems in diabetic neuropathic patients.

OBJECTIVE: To examine whether a reduced peripheral sensibility caused by diabetic neuropathy increases the attentional demands necessary for controlling and regulating gait. DESIGN: Nonrandomized control trial. SETTING: University motor performance laboratory. SUBJECTS: Twelve diabetic patients with peripheral neuropathy and 7 control subjects, all volunteers. INTERVENTIONS: All subjects first performed a control seated reaction time task. For the walking task, auditory stimuli were randomly presented in the third, fourth, or fifth walking cycle on left foot toe off on left foot heel contact. The subject's task was to respond verbally as fast as possible to the auditory stimulus, while maintaining progression. MAIN OUTCOME MEASURES: Simple reaction times and kinematics of the gait pattern (cycle amplitude, cycle duration, cycle speed, cadence and percentage of time spent in the single support phase) were evaluated. RESULTS: For the walking task, diabetic neuropathic patients had a smaller cycle amplitude, cycle speed, and percentage of time spent in the single support phase than control subjects. Also, reaction times while walking were higher for diabetic neuropathic patients than for control subjects. CONCLUSIONS: Diabetic neuropathic patients show a less destabilizing and more conservative gait than control subjects. The increased attentional demands in gait for the diabetic neuropathic patients, along with their more conservative gait pattern, suggest that a lack of proprioception from the legs affects the control of gait. Diminished sensory information makes gait control more cognitively dependent in diabetic neuropathic persons than in control subjects.

Aged↗
PubMed1995

Failure of 40 weeks of brisk walking to alter blood lipids in normolipemic women.

Sedentary, eumenorrheic women (N = 27) 22 to 40 years of age, with high baseline levels of plasma high-density lipoprotein cholesterol, were randomly assigned to a walking (n = 16) or a control group (n = 11). The training program involved treadmill walking 4.8 km (3.0 miles) four times a week for 40 weeks at a mean intensity of 72% maximal heart rate. Aerobic power (VO2max) was improved by 22%, but no training effect was observed in body composition variables or blood lipid/lipoprotein levels. Despite additional increments in exercise intensity over the final 20 weeks of training, most of the improvement in VO2max was observed over the first 20 weeks of the study. Exercising subjects' baseline levels of plasma HDL-C were found to be inversely associated with the change (delta) scores in the lipoprotein (r = -0.51, p < or = .05).

Adult↗
PubMed2005

Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review.

AIMS: The 6 min walk test (6MWT) is commonly used in clinical trials to assess treatments for heart failure, but its ability to distinguish between effective and ineffective treatments is questionable. The aim of this study is to investigate, using a systematic literature review, the utility of the 6MWT as a measure of the effectiveness of treatment in randomized controlled trials of heart failure. METHODS AND RESULTS: A literature search was performed using Medline, EMBASE, CINAHL, and Biological abstracts for randomized controlled trials that measured 6MWT between 1988 and 31 May 2004. A significant increase in 6MWT distance was observed in only 9 of 47 randomized controlled trials of pharmacological therapy; 2 of 6 trials of ACE-inhibitors; 3 of 17 trials of beta-blockers; 1 of 4 trials of digoxin; one trial of ibopamine; one trial of l-arginine; one trial of beriberine; and one trial showed superiority of captopril over flosequinan. A significant increase in 6MWT was observed in four out of six placebo-controlled trials of cardiac resynchronization. Smaller pharmacological trials with fewer centres were more likely to be positive; six out of nine positive pharmacological trials had four or less participating centres, raising the possibility of publication bias. Pharmacological trials including patients with more severe heart failure were more likely to show a significant improvement with therapy than trials of milder heart failure. Five out of seven pharmacological trials that reported an improvement in symptoms also reported an improvement in 6MWT distance. Of 30 pharmacological trials, 29 that reported no improvement in symptoms also reported no improvement in 6MWT. Using mean values in these trials, the age of patients appeared a more important determinant of 6MWT distance than New York Heart Association classification. CONCLUSION: The 6MWT has not yet been proven to be a robust test for the identification of effective pharmacological interventions although it appears useful for the assessment of cardiac resynchronization therapy. The results of the 6MWT were concordant with changes in symptoms, suggesting that it may be used as supportive evidence for symptom benefit. The test may be of greater value in patients with more advanced heart failure, where it may function as a maximal exercise test.

Cardiotonic Agents↗
PubMed2006

Effect of brisk walking in 1 or 2 daily bouts and moderate resistance training on lower-extremity muscle strength, balance, and walking performance in women who recently went through menopause: a randomized, controlled trial.

BACKGROUND AND PURPOSE: Menopause may induce a phase of rapid decreases in bone mineral density, aerobic fitness, muscle strength, and balance, especially in sedentary women. The purpose of this study was to examine the effects and feasibility of an exercise program of 1 or 2 bouts of walking and resistance training on lower-extremity muscle strength (the force-generating capacity of muscle), balance, and walking performance in women who recently went through menopause. SUBJECTS AND METHODS: The subjects were 134 women who recently went through menopause. The study was a 15-week, randomized, controlled trial with continuous and fractionated exercise groups. The outcomes assessed were lower-extremity muscle strength, balance, and walking time over 2 km. Feasibility was assessed by questionnaires, interviews, and training logs. RESULTS: One hundred twenty-eight women completed the study. Adherence to the study protocol was 92%. Both continuous and fractionated exercise groups improved equally in lower-extremity muscle strength and walking time but not in balance. Almost 70% of the subjects considered the program to be feasible. Two daily walking sessions caused fewer lower-extremity problems than did continuous walking. DISCUSSION AND CONCLUSION: Brisk walking combined with moderate resistance training is feasible and effective. Fractionating the walking into 2 daily sessions is more feasible than continuous walking.

Exercise↗
PubMed2005

The effectiveness of body weight-supported gait training and floor walking in patients with chronic stroke.

OBJECTIVE: To compare body weight-supported exercise on a gait trainer with walking exercise overground. DESIGN: Randomized controlled trial. SETTING: Rehabilitation hospital. PARTICIPANTS: Forty-five ambulatory patients with chronic stroke. INTERVENTIONS: Patients were randomized to 3 groups: (1) gait trainer exercise with functional electric stimulation (GTstim), (2) gait trainer exercise without stimulation (GT), and (3) walking overground (WALK). All patients practiced gait for 15 sessions during 3 weeks (each session, 20 min), and they received additional physiotherapy 55 minutes daily. MAIN OUTCOME MEASURES: Ten-meter walk test (10MWT), six-minute walk test (6MWT), lower-limb spasticity and muscle force, postural sway tests, Modified Motor Assessment Scale (MMAS), and FIM instrument scores were recorded before, during, and after the rehabilitation and at 6 months follow-up. RESULTS: The mean walking distance using the gait trainer was 6900+/-1200 m in the GTstim group and 6500+/-1700 m in GT group. In the WALK group, the distance was 4800+/-2800 m, which was less than the walking distance obtained in the GTstim group (P=.027). The body-weight support was individually reduced from 30% to 9% of the body weight over the course of the program. In the pooled 45 patients, the 10MWT (P<.001), 6MWT (P<.001), MMAS (P<.001), dynamic balance test time (P<.001), and test trip (P=.005) scores improved; however, no differences were found between the groups. CONCLUSIONS: Both the body weight-supported training and walking exercise training programs resulted in faster gait after the intensive rehabilitation program. Patients' motor performance remained improved at the follow-up.

Analysis of Variance↗
PubMed1992

DNA sequencing by a subcloning-walking strategy using a specific and semi-random primer in the polymerase chain reaction.

In its basic concept, in vitro DNA amplification by the polymerase chain reaction (PCR) is restricted to those instances in which segments of known sequence flank the fragment to be amplified. Recently, techniques have been developed for amplification of unknown DNA sequences. These techniques, however, are dependent on the presence of suitable restriction endonuclease sites. Here, we describe a strategy for PCR amplification of DNA that lies outside the boundaries of known sequence. It is based on the use of one specific primer, homologous to the known sequence, and one semi-random primer. Restriction sites in the 5' proximal regions of both primers allow for cloning of the amplified DNA in a suitable sequencing vector or any other vector. It was shown by sequence analysis that the cloned DNA fragments represent contiguous DNA fragments that are flanked at one side by the sequence of the specific primer. When omitting the semi-random primer, a single clone was obtained, which originated from PCR amplification of target DNA by the specific primer in both directions.

Base Sequence↗
PubMed2002

[Current status of endovascular therapy in the femoropopliteal vascular segment in chronic peripheral arterial occlusive disease].

Technical success of endovascular measures in the femoropopliteal region has increased since the introduction of new technology (hydrophilic guide-wires, stents, stent grafts) in the last decade to rates of more than 90%. If the initial revascularization--even of long segment occlusions--is successful, the modern armamentarium of interventional radiology enables to keep the vessel open acutely. Evidence, that the immediate success of revascularization leads to a continuous improvement of the clinical symptoms, measured by clinically relevant end points (e.g. improvement of walking distance, increase of limb salvage, increase of survival), has yet to be shown. Several prospective randomized trials demonstrated improvement of walking distance after one year follow-up, but not after two years follow-up in patients with chronic femoropopliteal obstructions, who were treated with PTA compared to walking exercise only. The only two prospective randomized trials comparing vascular surgery and endovascular therapy for femoropopliteal obstructions could not demonstrate any advantage of one of the two modalities in patients with claudication or critical ischemia. The transatlantic consensus document (TASC) recommends PTA as therapy of choice in the femoropopliteal arteries only for single stenosis < 3 cm and does not recommend primary stenting. In order to evaluate endovascular therapy in the femoropopliteal region outcome studies are needed, which carefully assess clinically relevant end points like improvement of walking distance, limb salvage, and survival, but also disease specific quality of life evaluations. Several meta-analyses, performed in recent years, have demonstrated that endovascular therapy has a definite role in the femoropopliteal segment. However, the particular role has to be evaluated for the individual clinical case in the light of case-specific findings and symptoms.

Angioplasty, Balloon↗
PubMed1995

Energy expenditure during submaximal walking with Exerstriders.

This study was designed to determine whether Exerstriding, a modified form of walking using walking sticks (Exerstriders), resulted in an augmented cardiorespiratory response and a greater energy expenditure than when walking without Exerstriders. Female subjects (23.6 +/- 4.0 yr; 58.5 +/- 5.5 kg) completed two randomly assigned trials of treadmill walking (6.7 km.h-1; 0% grade; 30 min.) with (Exerstrider (E)) and without Exerstriders (Control (C)). Mean oxygen consumption (E = 20.5 +/- 1.2 ml.min-1.kg-1; C = 18.3 +/- 2.5 ml.min-1.kg-1), heart rate (E = 132.5 +/- 19.2 beats.min-1; C = 121.5 +/- 21.2 beats.min-1) and respiratory exchange ratio (E = .82 +/- .03; C = .78 +/- .04) were significantly greater (P < or = 0.05) while walking with Exerstriders. Total caloric expenditure was also significantly greater during the Exerstrider condition (E = 173.7 +/- 20.9 kcal; C = 140.7 +/- 27.2 kcal.). In contrast, the rating of perceived exertion did not differ significantly between the two conditions. These data suggest that Exerstriding provides a means to increase caloric expenditure during submaximal walking, a factor that may be of critical importance in enhancing health benefits--such as improved body composition and aerobic capacity--typically associated with walking programs.

Adult↗