Biomedical subjects
Publications and source records attributed to D A Gabriel.
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Experimental investigation of practicing a dynamic, goal-directed movement reveals significant changes in kinematics. Modeling can provide insight into the alterations in muscle activity, associated with the kinematic adaptations, and reveal the potential motor unit (MU) firing patterns that underlie those changes. In this paper, a previously developed muscle model and software (Raikova and Aladjov, Journal of Biomechanics, 35, 2002) have been used to investigate changes in MU control, while practicing fast elbow flexion to a target in the horizontal plane. The first trial (before practice) and the last trial (after extensive practice) of two subjects have been simulated. The inputs for the simulation were the calculated external moments at the elbow joint. The external moments were countered by the action of three flexor muscles and two extensor ones. The muscles have been modeled as a mixture of MUs of different types. The software has chosen the MU firing times necessary to accomplish the movement. The muscle forces and MUs firing statistics were then calculated. Three hypotheses were tested and confirmed: (1) peak muscle forces and antagonist co-contraction increase during training; (2) there is an increase in the firing frequency and the synchronization between MUs; and (3) the recruitment of fast-twitch MUs dominates the action.
OBJECTIVE: To assess the multidirectional force and indwelling electromyographic activity during maximal effort isometric actions of the neck. DESIGN: A descriptive study involving maximal effort isometric actions of the neck and bilateral electromyographic activity. BACKGROUND: This study extends previous efforts to assess the isometric strength of the neck, but with greater precision with respect to the intermediate angles between the frontal and sagittal planes. METHODOLOGY: Participants (n = 18) generated a maximal isometric force in twelve directions in the horizontal plane. All exertions were realized in neutral position. A load cell measured forces and intramuscular fine-wire electrodes were used to record the bilateral electromyographic activity of the sternocleidomastoid, scalenus medius, trapezius (middle fibers), semispinalis capitis, and splenius capitis. RESULTS: Strength in the anterolateral directions were similar, but exhibited right lateral dominance in extension. The sternocleidomastoid and trapezius (middle fibers) exhibited bilateral symmetry while the scalenus medius, semispinalis capitis, and splenius capitis did not. Furthermore, the agonist, synergist, and antagonist action of the individual muscles was clear. The direction of force that resulted in the greatest electromyographic activity was consistent with what has been shown in anatomy texts. This was not true for the scalenus medius. We showed that the scalenus medius contributes to extension, with synergistic activity in the lateral bending direction. CONCLUSIONS: The greater precision revealed novel information about the isometric strength of the neck and its musculature.
OBJECTIVE: This study examined the intraclass reliability of different measures extracted from Hoffmann reflex (H-reflex) stimulus-response curve that are used to assess neuromuscular excitability. The following measures were compared: (1) the peak-to-peak amplitude of the H-reflex at a stimulus intensity associated with 5% of the maximum M-wave; (2) the slope of the regression line of the H-reflex stimulus-response curve; and (3) the peak of the first derivative of the H-reflex stimulus-response curve, a new measure introduced in this paper. METHODS: The H-reflex was elicited in the soleus for 24 subjects (12 males and 12 females) on 5 separate days. Vibration was applied to the Achilles tendon prior to stimulation to test the sensitivity of the measures on test day 4. The stimulus intensity was gradually increased from below the threshold for an H-reflex response to above the maximum M-wave (Mmax) response. The means of 5 evoked potentials at each intensity level were used to create both the H-reflex and M-wave stimulus-response curves for each subject across test days. Determination of reliability involves the consideration of both the stability and consistency of the measures. A repeated measures analysis of variance evaluated the stability of the group means across test sessions. The consistency of scores within individuals was determined by calculating the intraclass correlation coefficient (ICC). Calculation of the 95% confidence interval of estimation was used to assess significant differences between ICCs. RESULTS: The H-reflex measures were both stable and consistent across the first 3 test days. Achilles tendon vibration resulted in a profound reduction (59-70%) on test day 4, and then there was a return to baseline levels on test day 5. The ICC for H-reflex at a stimulus intensity associated with 5% of the maximum M-wave was 0.85. The ICC for the slope of the regression line of the H-reflex stimulus-response curve was 0.79, while it was 0.89 for the peak of the first derivative of the H-reflex stimulus-response curve. However, there was no statistical significance (P>0.05) between the 3 EMG measures of the H-reflex arc. Maximum M-wave amplitude had an ICC of 0.96 attesting to careful methodological controls. CONCLUSIONS: The peak of the first derivative of the H-reflex stimulus-response curve was shown to have comparable sensitivity and reliability as other more established measures. SIGNIFICANCE: The first derivative of the H-reflex stimulus-response curve provides the rate of change, rather than amplitude, making it a robust measure of reflex arc excitability. The higher ICC for the first derivative offers greater statistical power, which is of practical significance.
The studies reported here show that factor (F)VIIa can activate factor (F)IX on activated platelets in the absence of tissue factor. Both FIX and FIXa bind to the activated platelet surface with a K(d) of 8 nM and 2 nM, respectively. With factor (F)VIIIa, FIXa binds more tightly to platelets (K(d) 0.6 nM). At rFVIIa concentrations < 100 nm, no direct binding to the activated platelet surface can be detected with electrophoretic light scattering. However, in the presence of FIX, rFVIIa binding to platelets at concentrations as low as 10 nm rFVIIa can be detected. This is reflected by a decrease in the FIX K(d) from 8 to 1.6 nM. When rFVIIa is added to activated platelets in the presence of both FIX and FVIIIa, the K(d) for FIX decreases to 0.6, suggesting that rFVIIa activates FIX on the surface of activated platelets in the absence of tissue factor. The activation of FIX by FVIIa on activated platelets can also be demonstrated by a functional assay for FIXa. These data show that pharmacological doses of rFVIIa result in the direct activation of FIX by rFVIIa to form additional tenase complexes ultimately resulting in improved thrombin generation. These results may explain, at least in part, the mechanism of action of rFVIIa in hemorrhagic conditions seen in otherwise normal patients who develop an acquired coagulopathy due to trauma, surgery or a variety of other events in which rFVIIa has been found to be effective.
Fibrin clot structure studies are often performed using optical methods. For example, the clot's fiber structure can be assessed by measuring light scattering as a function of wavelength. From these measurements, one can calculate the mass/length ratio (mu), a relative measure of fibrin thickness. Fiber thickness has important functional correlates in terms of clot stability and resistance to fibrinolysis. Typically, measurements to calculate mass/length ratios are carried out on high-end spectrophotometers. However, limitations of this instrument include the large sample volume required and the inability to read multiple samples at one time. To circumvent these limitations, a plate-reading spectrophotometer is more commonly used to monitor clot formation; increases in absorbance indicate clot formation, while decreases indicate clot lysis. However, it is unclear whether plate-reading spectrophotometers can be used to quantitatively evaluate fibrin fiber structure. In the current study, we compared spectrophotometric analysis of fibrin gels on single-sample and plate-reading spectrophotometers. Results show that a plate-reading spectrophotometer does not give accurate measurements of the fiber mass/length ratio. However, the plate-reading spectrophotometer can provide a qualitative measure of fiber structure for both purified fibrinogen and plasma. We suggest that plate-reading spectrophotometers can provide a convenient, rapid, and inexpensive means of analyzing fibrin clot structure.
This study monitored the effects of a short-term elbow flexor training program on surface electromyographic (SEMG) spike activity. The experimental paradigm consisted of three test sessions separated by 2-week intervals. At the beginning of each session, participants (N=13) performed five maximal effort isometric contractions of the elbow flexors to serve as baseline. After 5 min of rest, the participants then engaged in a 30-trial isometric fatigue protocol during which maximal elbow flexion torque was measured with a load-cell, and the maximal rate of change in the torque (dtau/dt(max)) was obtained from the differentiated torque-time curve. Bipolar electrodes were used to monitor the SEMG spike activity of the biceps brachii. Mean spike amplitude (MSA) and mean spike frequency (MSF) were calculated for the torque development and constant-torque phases of the isometric contraction, termed Segment 1 and Segment 2, respectively. Mean power frequency (MPF) was also calculated for Segment 2. The five baseline contractions of the second and third sessions were compared with those of the first session and analyzed for training-related changes. Training increased dtau/dt(max) but failed to change maximal elbow flexion torque or MSA. However, there was an increase in the MSF during the torque development phase of the contraction (Segment 1). Both MSA and MSF were greatest during the constant-torque phase of the isometric contraction (Segment 2). There was a strong linear correlation (r=0.90, P<0.05) between MSF and MPF during (Segment 2). We hypothesize that the increase in dtau/dt(max) is due to enhanced motor-unit rate-coding. The demonstrated correlation between MSF and MPF measures will allow investigators to use spike analysis to examine the frequency content of the SEMG signal under non-stationary conditions.
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OBJECTIVE: The present study was designed to test the effects of the reversal of antagonists on the peak rate of tension development (dF/dt(max)) of the elbow extensors. DESIGN: Experimental, with matched controls. SETTING: A biomechanics research laboratory. PARTICIPANTS: Twenty-six healthy women without a history of upper extremity injury or neurologic disorder, randomly assigned to experimental (n = 13) or control (n = 13) groups. INTERVENTIONS: Two groups of healthy subjects followed identical exercise protocols, except that the control group performed maximal isometric contractions of the elbow extensors and the experimental group executed a maximal isometric elbow flexion contraction immediately before a maximal elbow extension contraction. Both groups performed 5 cycles of a 2-second contraction with 22-second rest periods between agonist muscle contractions and were evaluated at 4 test sessions spaced 2 weeks apart. MAIN OUTCOME MEASURES: All measurements were done with the shoulder and elbow at 90 degrees of flexion in the sagittal plane to ensure reproducibility. A load cell was used to measure elbow extension moment and to calculate the peak rate of tension development (dF/dt(max)). Biceps and triceps brachii surface electromyographic activity was monitored concurrently. The electromyographic measures were mean spike (peak-to-peak) amplitude and mean spike frequency of the biceps and triceps brachii activity. RESULTS: Intraclass dF/dt(max) and electromyographic reliability was good (r > or = .72) in both groups. Because biceps electromyographic measures were considerably less reliable (r < or = .53), they were not included in our analysis. While dF/dt(max) increased quadratically in both groups (p <.05), the experimental group was on average 36.1Nm. s(-1) (63%) greater across sessions 2 to 4 (p <.05). In contrast, triceps electromyographic activity did not differ significantly between groups (p >.05). The means averaged across groups exhibited a quadratic increase from session 1 to session 4: 91microV or 48% for mean spike amplitude (p <.05) and 7Hz or 16% for mean spike frequency (p <.05). CONCLUSIONS: The greater dF/dt(max) for the experimental group was not associated with increased electromyographic activity. The experimental group appeared to use the biomechanic properties of the pretensioned extensor muscle-tendon complex, rather than neurologic biasing, to accomplish its power gains.
The assembly of the tenase complex on the surface of the platelet is an essential step in maintaining normal hemostasis as evidenced by the serious hemorrhagic diathesis associated with either factor IX (FIX) or factor VIII deficiencies. Understanding the regions and or residues of FIX crucial for proper binding to platelets has important clinical implications. The ability of FIX to bind activated platelets in the presence of 4 mmol/l CaCl2 was examined using electrophoretic light-scattering experiments. Wild-type FIX binds to activated platelets with dissociation constant Kd = 7.9 nmol/l. Activated FIX binds to activated platelets with Kd = 2 nmol/l. Activated factor VII does not bind activated platelets at physiological concentrations. The Gla domain of FIX is important for the binding of FIX to activated platelets since a chimera with a factor VII (FVII) template and FIX Gla [FVII(FIXGla)] has Kd = 9.6 nmol/l, and a chimera with a FVII template and FIX Gla, A and the first epidermal growth factor domain (EGF1) [FVII(FIXGla,A,EGF1)] has Kd = 9.7 nmol/l, but a chimera with a FIX template and a FVII Gla [FIX(FVIIGla)] does not bind activated platelets. Altering the fifth residue of FIX from a lysine to an alanine (Lys5<--Ala) abolishes the mutant from binding to collagen but does not affect FIX binding to the activated platelet (Kd = 9.8 nmol/l). Point mutations involved with residues 4 and 5 (Gly4<--Phe and Lys5<--no residue), residue 9 (Phe9<--Ala), residue 10 (Val10<--Lys) and residues 9-11 (Phe9<--Met, Val10<--Lys, Glu11<--Lys) do not bind to activated platelets.
PURPOSE: This paper investigates the neural mechanisms responsible for the increase in strength that occurs during serial isometric contractions. METHODS: A three-session design was used. Thirteen subjects (N = 13) were asked to perform five maximal isometric elbow extension strength trials to serve as baseline. After a 5-min rest, the subjects were administered a 30-trial fatigue protocol. This process was repeated two more times at 2-wk intervals. Elbow extension torque and surface electromyography (EMG) of the triceps and biceps brachii were monitored concurrently. The criterion measures were elbow extension torque, root-mean-square EMG amplitude, and mean power frequency (MPF). RESULTS: Intraclass reliability ranged from good to excellent. Within each experimental session, the fatigue protocol resulted in a decrease in maximal isometric elbow extension torque as well as biceps and triceps EMG amplitude and MPF (P < 0.05). However, the mean of the 30 trials and the magnitude of the linear decrease in elbow extension torque increased across the three sessions (P < 0.05). Biceps and triceps EMG amplitude increased and MPF decreased as the number of sessions increased (P < 0.05). CONCLUSIONS: These findings suggest that the fatigue protocol served as a training stimulus to down regulate motor-unit firing frequency.
HLA-identical bone marrow or stem cell transplantation from a sibling is the preferred treatment for patients with chronic myelogenous leukemia, bone marrow failure syndromes, relapsed acute leukemia, and specific inborn errors of metabolism. Several groups have shown that granulocyte colony-stimulating factor (G-CSF)--mobilized peripheral blood progenitor cells (PBPCs) obtained from HLA-matched siblings are effective in reconstitution of marrow function after marrow ablative conditioning therapy. To evaluate whether G-CSF treatment before bone marrow harvest leads to enhanced recovery of PBPC counts and recovery from limited graft-versus-host disease (GVHD), we assessed the outcome of a sequential cohort of patients treated identically and then given either G-CSF--mobilized PBPCs or G-CSF--stimulated bone marrow from HLA-identical siblings. We show that the time to neutrophil engraftment is identical in the 2 cohorts, whereas platelet engraftment is earlier with the use of PBPCs. The incidence of acute GVHD was decreased, and that of chronic GVHD significantly decreased, in the group receiving bone marrow. Overall survival was not different between the 2 groups. Thus, G-CSF--stimulated bone marrow offers a source of stem cells that allows for early neutrophil engraftment with a decreased risk of GVHD.
The purpose of this study was to investigate whether storing mobilized peripheral blood progenitor cell (PBPC) collections overnight before CD34+ selection may delay platelet count recovery after high-dose chemotherapy and CD34+-enriched PBPC re-infusion. Lymphoma patients underwent PBPC mobilization with cyclophosphamide 4 g/m2 i.v. and G-CSF 10 microg/kg/day subcutaneously. Patients were prospectively randomized to have each PBPC collection enriched for CD34+ cells with the CellPro CEPRATE SC System either immediately or after overnight storage at 4 degrees C. Thirty-four patients were randomized to overnight storage and 34 to immediate processing of PBPC; 15 were excluded from analysis due to tumor progression or inadequate CD34+ cell mobilization. PBPC from 23 patients were stored overnight, while 30 subjects underwent immediate CD34+ selection and cryopreservation. Median yield of CD34+ enrichment was 43.6% in the immediate processing group compared to 39.1% in the overnight storage group (P = 0.339). Neutrophil recovery >500 x 10(9)/l occurred a median of 11 days (range 9-16 days) in the overnight storage group compared to 10.5 days (range 9-21 days) in the immediate processing group (P = 0.421). Median day to platelet transfusion independence was 13 (range 7-43) days in the overnight storage group vs 13.5 (range 8-35) days in those assigned to immediate processing (P = 0.933). We conclude that storage of PBPC overnight at 4 degrees C allows pooling of consecutive-day collections resulting in decreased costs and processing time without compromising neutrophil and platelet engraftment after infusion of CD34+-selected progenitor cells. Bone Marrow Transplantation(2000) 25, 559-566.
The effect of practice on predicting elbow flexion movement time was studied. Participants (N = 18) performed 400 elbow flexion trials to a target in the horizontal plane. The trials were distributed equally over four sessions. The goal was to decrease the movement time (MT) for the same degree of accuracy. The electromyographic (EMG) activity of the biceps and triceps brachii was monitored with standard Beckman Ag/AgCl surface electrodes. The EMG measures formed two variable sets within one prediction equation. One variable set was composed of the onset of muscle activity relative to the start of movement (motor time) and the duration of muscle activity. The other variable set consisted of the mean amplitude value of the entire burst and of the first 30 ms (Q30) of activity. As the maximal speed of limb movement increased, the duration of muscle activity (motor time and EMG duration) decreased, and the magnitude of muscle activity (MAV and Q30) increased. Most of the change in the duration of muscle activity occurred in Session 1, while the magnitude of muscle activity continued to increase until Session 3. Multiple regression analysis revealed a cooperative strategy between the magnitude and duration of muscle activity. Early in learning, participants adjusted the magnitude of muscle activity to increase limb movement speed. As practice continued, alterations in the duration of muscle activity became more important, while the magnitude changes were less involved. Late in learning, both dimensions of muscle activity were used to decrease MT. We suggest that the interplay between the magnitude and duration of muscle activity may be due to: (a) cognitive factors related to the division of attention in a motor skill, (b) an increase in the frequency of motor unit firing that affects both dimensions of muscle activity, or (c) some combination of (a) and (b).
A global assessment of hemostasis can be determined by the perfusion of unanti-coagulated whole blood through a hollow fiber at a nominal shear rate of 300 sec(-1). Once the pressure across the hollow fiber is stable, uniform holes are punched through the top and bottom of the fiber, resulting in an optically detectable leakage of blood from the hollow fiber and a pressure drop throughout the system. Changes in the shear rate and flow profile at the puncture site are sufficient to activate platelets mechanically, resulting in a platelet plug observable by electron microscopy. Fibrin is the principal component of the luminal surface adjacent to the puncture site and a prominent fibrin tail extends downstream from this site. The time from the introduction of the punch site to 90% recovery of the baseline pressure defines the in vitro bleeding time (IVBT). The rate of the pressure recovery appears to be related to the efficiency of the thrombin-mediated recruitment of additional platelets to the plug. Pressure recovery can be delayed by either platelet or thrombin inhibitors.
Although heparin and some radiographic contrast agents inhibit coagulation, thrombi can still form in their presence. The chemical environment in which a thrombus forms affects fibrin structure that may alter the ability of the thrombus to be lysed. Therefore, we assessed changes in fibrin structure in 13 patients referred for coronary angiography. Blood was obtained from the femoral vein, femoral artery, ascending aorta, left main coronary artery (LMCA), and coronary sinus (CS) before, during, and after coronary angiography was performed with iohexol. The number of fibrin monomers per fiber cross section was determined by turbidity measurements of fibrin gels formed from plasma samples. At baseline there was no difference in the number of fibrin monomers per fiber cross section in plasma gels generated from the different sampling sites. After iohexol administration, there was a significant decrease in the number of fibrin monomers per fiber cross section at the sampling sites ranging from - 13% to -25% compared with the respective baseline values with the largest change in the LMCA CS (51+/-16 to 38+/-15, p <0.025). Transcardiac (LM - CS value) changes in the number of fibrin monomers per fiber cross section were dependent on the timing of the sample collection in the CS. In 7 patients, the CS sample was collected approximately 2 minutes after injection of contrast material and there was no transcardiac difference. When the CS sample was obtained during contrast injection (n=6) a large transcardiac change occurred (44+/-10 to 32+/-14, p=0.01). These data show transient changes in fibrin structure during coronary angiography with iohexol. The thinner fibers formed in the presence of iohexol were more resistant to fibrinolysis.
The binding of the multidomain protein factor VIIa (fVIIa) to tissue factor provides the interprotein communication necessary to make fVIIa an efficient catalyst of the initial event in the extrinsic pathway of blood coagulation. We have investigated the stability of individual domains in fVIIa and the influence of Ca2+ and an irreversible active-site inhibitor (FFR-chloromethyl ketone). Equilibrium guanidine hydrochloride (GuHCl)-induced unfolding monitored by tryptophan fluorescence and far-UV circular dichroism (CD) demonstrated that the gamma-carboxyglutamic acid (Gla) domain unfolds at 0.3 M GuHCl and the serine protease (SP) domain at 3 M GuHCl and that Ca2+ is a prerequisite for the formation of an ordered, compact structure in the Gla domain. The loss of amidolytic activity coincides with the first transition, which is stabilized by the active-site inhibitor, and a change in the environment of the active site is demonstrated using a fluorescent inhibitor (DEGR-chloromethyl ketone). Thermal unfolding monitored by differential scanning calorimetry (DSC) reveals that Ca2+ stabilizes the SP domain slightly, increasing the unfolding temperature by 2.7 degrees C. In addition, Ca2+ is required for a large enthalpy change concomitant with unfolding of the Gla domain, and this unfolding enthalpy is only detectable in the presence of the SP domain, indicating some kind of interaction between these domains. Thermal unfolding measured by CD indicates secondary structural changes at the same temperature as the heat absorption in the DSC but only when both the Gla domain and the SP domain are present together with Ca2+ ions. Taken together, these results indicate a Ca2+-dependent interaction between the Gla domain and the SP domain, implying a high degree of flexibility of the domains in free fVIIa. It is also shown that the epidermal growth factor-like domains are stable at elevated temperatures and high GuHCl concentrations. Moreover, already at physiological temperature, subtle structural changes take place which influence the overall shape of fVIIa and are detrimental to its enzymatic activity.
The effect of repeated maximal effort isotonic contractions on electromechanical delay was studied. Over 4 days, 17 male subjects performed 400 rapid elbow flexion trials. The kinematics and surface electromyographic (EMG) activity of the biceps brachii of these subjects were recorded. The period from the onset of the EMG until the beginning of movement was defined as the electromechanical delay. The period from the beginning of movement until the end of the EMG was defined as the second component of the contraction. Over the 4 day period there was an increase in the speed of limb movement. The mean power frequency and the duration of the EMG during the electromechanical delay did not change, while the root-mean-square amplitude increased. The duration of the EMG during the second component of the contraction remained stable. The mean power frequency and the root-mean-square amplitude of the EMG during the second component of the contraction increased with the speed of limb movement. We conclude that the faster contractions were a result of changes in motor unit recruitment during the second component of the contraction, rather than in the electromechanical delay.