Control of finger grip forces in overarm throws made by skilled throwers.

In an overarm throw, as the hand opens and the ball rolls along the fingers, the ball exerts a back force on the fingers. Previous studies suggested that skilled throwers compensate for this back force by producing an appropriate finger flexor torque to oppose the back force, but it was unclear how this is controlled by the CNS. We investigated whether the increase in finger flexor torque is timed precisely to occur late in the throw as the fingers open or whether the increase occurs throughout the throw to anticipate the increase in hand acceleration. Recreational ball players threw balls of different weights and diameters at different speeds from both a sitting and standing position while arm joint rotations were recorded with the search-coil technique. Force transducers were taped to the distal and middle phalanges of the middle finger and subjects released the ball from this finger. Passive forces on the finger were also recorded in "fake" throws in which the ball was taped to the finger and subjects did not grip the ball. These skilled throwers correctly anticipated the magnitude of the back force from the ball on the finger because the mean amplitude of finger extension did not increase in throws made with a large range of increasing back forces. This was achieved by subjects gripping the ball during the backswing with a force proportional to ball weight and intended ball speed (acceleration) and progressively increasing the grip force throughout the backswing and forward throw. The magnitude of this grip force during the forward throw was not affected by ball texture. After ball release from the fingertip, the finger flexed in proportion to the peak force on the finger before ball release. It is concluded, in a skilled fast overarm throw where large, fast-changing forces on the fingers result from the sum of motions at all arm joints, that finger flexor torque is progressively increased throughout the throw in an anticipatory (predictive) fashion to counteract the progressively increasing back force from the ball.     

Finger opening in an overarm throw is not triggered by proprioceptive feedback from elbow extension or wrist flexion

 Accuracy in an overarm throw requires great precision in the timing of finger opening. We tested the hypothesis that finger opening in an overarm throw is triggered by proprioceptive feedback from elbow extension or wrist flexion. The hypothesis was tested in two ways: first, by unexpectedly perturbing elbow extension or slowing wrist flexion and determining whether changes occurred in finger opening, and second, by measuring the latency from the start of these joint rotations to the start of finger opening. Subjects threw balls fast and accurately from a sitting or standing position while joint rotations were recorded with the search-coil technique. Elbow extension was unexpectedly blocked near the start of forward motion of the hand by a rope attached to the wrist that passed through a catch mechanism located behind the subject. In spite of a slowing or complete block of elbow extension, and in some cases a replacement of elbow extension by elbow flexion, finger opening always occurred and at the same latency as for normal throws. Wrist flexion was slowed in seven of eight subjects when subjects changed from throwing with a light ball (14 g, 70 mm diam.) to a heavy ball (210 g, 65 mm diam.). For the first throw with the heavy ball, this slowing was neither fully anticipated by the subject nor compensated for by the changed proprioceptive feedback associated with the slowing. Consequently, the timing of finger opening was unchanged and (to the surprise of the thrower) the ball went high. Furthermore, in unperturbed throws with tennis balls, the latency from onset of wrist flexion or elbow extension to onset of finger opening was too short for either to have triggered finger opening (across subjects means were 4 ms for wrist flexion and 21 ms for elbow extension). In additional analysis, no relation was found between the time of onset of earlier occurring rotations at the shoulder and the time of onset of finger opening. We concluded that, although a role for all proprioceptive feedback in triggering finger opening cannot be disproved by these experiments, it can be ruled out for feedback arising from elbow extension and wrist flexion, and it seems unlikely for feedback arising from events occurring very early in the throw. The more likely possibility is that finger opening in an overarm throw is triggered by a central command based on an internal model of hand trajectory. Received: 6 July 1998 / Accepted: 16 October 1998     

Timing of finger opening and ball release in fast and accurate overarm throws

How precisely does the CNS control the timing of finger muscle contractions in skilled movements? For overarm throwing, it has been calculated that a ball release window of less than 1 ms is needed for accuracy in long throws. The objective was to investigate the timing precision of ball release and finger opening for 100 overarm throws made using only the arm. Subjects sat with a fixed trunk and threw balls fast and accurately at a 6-cm-square target when it was 1.5, 3.0 and 4.5 m away. Three-dimensional angular positions in space of the clavicle, upper arm, forearm, hand and distal phalanx of the middle finger were simultaneously recorded at 1000 Hz using the magnetic-field search-coil technique. Ball release was determined by pressure-sensitive microswitches on the proximal and distal phalanges of the middle finger (proximal and distal triggers). Variability of ball release, defined in terms of the standard deviation (SD) of the means of release times, was different when synchronized to different hand kinematic parameters. It was highest to the start of movement (when the hand started rotating vertically forward and up around a space-fixed horizontal axis) and was lowest when synchronized to the moment near ball release when the hand was vertical. These values did not depend on target distance. When throws were synchronized to vertical hand position, and SDs were averaged across the 10 subjects, the average interval for 95% of the throws (4×SD) was 9.6 ms for ball release and 10.0 ms for onset of finger opening. Thus, two independent measures of timing precision gave similar results. It is concluded that for 100 fast and accurate throws made by male recreational ball players, timing of finger opening and ball release was controlled precisely but not to fractions of a millisecond.     

Failure of cerebellar patients to time finger opening precisely causes ball high-low inaccuracy in overarm throws.

We investigated the idea that the cerebellum is required for precise timing of fast skilled arm movements by studying one situation where timing precision is required, namely finger opening in overarm throwing. Specifically, we tested the hypothesis that in overarm throws made by cerebellar patients, ball high-low inaccuracy is due to disordered timing of finger opening. Six cerebellar patients and six matched control subjects were instructed to throw tennis balls at three different speeds from a seated position while angular positions in three dimensions of five arm segments were recorded at 1,000 Hz with the search-coil technique. Cerebellar patients threw more slowly than controls, were markedly less accurate, had more variable hand trajectories, and showed increased variability in the timing, amplitude, and velocity of finger opening. Ball high-low inaccuracy was not related to variability in the height or direction of the hand trajectory or to variability in finger amplitude or velocity. Instead, the cause was variable timing of finger opening and thereby ball release occurring on a flattened arc hand trajectory. The ranges of finger opening times and ball release times (timing windows) for 95% of the throws were on average four to five times longer for cerebellar patients; e.g., across subjects mean ball release timing windows for throws made under the medium-speed instruction were 11 ms for controls and 55 ms for cerebellar patients. This increased timing variability could not be explained by disorder in control of force at the fingers. Because finger opening in throwing is likely controlled by a central command, the results implicate the cerebellum in timing the central command that initiates finger opening in this fast skilled multijoint arm movement.     

Increased variability in finger position occurs throughout overarm throws made by cerebellar and unskilled subjects.

We investigated the ability of cerebellar patients and unskilled subjects to control finger grip position and the amplitude of finger opening during a multijoint overarm throw. This situation is of interest because the appropriate finger control requires predicting the magnitude of back forces from the ball on the finger throughout the throw and generating the appropriate level and rate of change of finger flexor torque to oppose the back force. Cerebellar patients, matched controls, and unskilled subjects threw tennis balls and tennis-sized balls of different weights. In all cases angular positions of five arm segments in three dimension were recorded at 1,000 Hz with the search-coil technique as subjects threw from a seated position. When the hand was stationary, cerebellar patients showed a normal ability to grip the ball and open the fingers and drop the ball. In contrast, in overarm throws where a back force occurred on the fingers, cerebellar patients showed an abnormally large variability in amplitude of the change in finger position when gripping, in amplitude of finger opening, and in amplitude of the change in finger position 10 ms after ball release. This was not due to more trial-to-trial variation in throwing speed. When throwing balls of increasing weights, both controls and cerebellar patients had increasing finger flexions after ball release that indicated that, on average, both scaled finger force in proportion to ball weight during the throw. Unlike skilled controls, cerebellar patients showed a small (<20 degrees ) increase in the amplitude of finger opening with balls of increasing weight. However, neither the increase in variability of finger position nor the increase in finger amplitude with balls of increasing weight were unique cerebellar signs because both were observed to various degrees in unskilled throwers. It is concluded that in the absence of either normal cerebellar function or skill, the central neural activity that controls finger opening in throwing can increase finger flexor force to oppose an increase in back force from heavier balls and can open the fingers but cannot control finger force or finger opening precisely and consistently from throw to throw. These results fit with the idea that cerebellar disorders are greater in multijoint than single-joint movements because control of force is more complicated. They are also consistent with the hypothesis that the cerebellum produces skill in movement by reducing variability in the timing and force of muscle contractions.     

An analytical model for the investigation of axial wall forces generated by an arterial stenosis.

The causes of arteriosclerosis are intensively investigated since many decades. While circumferential wall stress has received a lot of attention, axial stress (also called "longitudinal" stress) has been largely neglected, and practically never incriminated. However, it has been suggested in 2003 that moderate and severe arterial stenoses may induce non negligible axial forces cyclically in the vessel segment just proximal to the constriction cone. In the present contribution, we describe a simple analytical model that allows to study the distribution of these forces along the vessel in dependence of the respective axial elasticities of vessel and surrounding tissues, and of the stenosis length.     

Residual control of isometric finger forces in hemiparetic patients. Evidence for dissociation of performance deficits

Dissociation of performance in the control of isometric finger forces was observed in 6 patients with left-sided unilateral lesions involving sensorimotor areas. In a precision task subjects had to maintain, under visual feedback, a low constant force (2.5 N) while holding a force transducer between thumb and index finger. Performance was compared with that in a speed task, where changes had to be produced, as rapidly as possible, between two prescribed forces (6.25 and 18.75 N). While there were severe deficits in fast force changes corresponding to the functional impairment of the right hand in all patients, right hand maintenance of low isometric force remained intact in the same patients.     

Thumb and finger forces produced by motor units in the long flexor of the human thumb

The uncommonly good proprioceptive performance of the long flexor of the thumb, flexor pollicis longus (FPL), may add significantly to human manual dexterity. We investigated the forces produced by FPL single motor units during a weak static grip involving all digits by spike-triggered averaging from single motor units, and by averaging from twitches produced by intramuscular stimulation. Nine adult subjects were studied. The forces produced at each digit were used to assess how forces produced in FPL are distributed to the fingers. Most FPL motor units produced very low forces on the thumb and were positively correlated with the muscle force at recruitment. Activity in FPL motor units commonly loaded the index finger (42/55 units), but less commonly the other fingers ( P < 0.001). On average, these motor units produced small but significant loading forces on the index finger (∼5.3% of their force on the thumb) with the same time-to-peak force as the thumb (∼50 ms), but had no significant effect on other fingers. However, intramuscular stimulation within FPL did not produce significant forces in any finger. Coherence at 2–10 Hz between the thumb and index finger force was twice that for the other finger forces and the coherence to the non-index fingers was not altered when the index finger did not participate in the grasp. These results indicate that, within the long-term coordinated forces of all digits during grasping, FPL motor units generate forces highly focused on the thumb with minimal peripheral transfer to the fingers and that there is a small but inflexible neural coupling to the flexors of the index finger.     

Primary care compensation at an academic medical center: a model for the mixed-payer environment.

The authors' academic medical center, Brigham and Women's Hospital, Boston, Massachusetts, developed a primary care physician (PCP) salary incentive program for employed academic physicians. This program, first implemented in 1999, was needed to meet the financial imperatives placed on the institution by managed care and the Balanced Budget Act of 1997; its goal was to create a set of incentives for PCPs that is consistent with the mission of the academic center and helps motivate and reward PCP's work. The program sought to simultaneously increase productivity while optimizing resource utilization in a mixed-payer environment. The salary incentive program uses work relative-value units (wRVUs) as the measure of productivity. In addition to productivity-derived base pay, bonus incentives are added for efficient medical management, quality of care, teaching, and seniority. The authors report that there was significant concern from several members of the physician staff before the plan was implemented; they felt that the institution's PCPs were already operating at maximum clinical capacity. However, after the first year of operation of this plan, there was an overall 20% increase in PCP productivity. Increases were observed in all PCP subgroups when stratified by professional experience, clinical time commitment, and practice location. The authors conclude that the program has succeeded in giving incentives for academic PCPs to achieve under the growing demands for revenue self-sufficiency, managed care performance, quality of care, and academic commitment.     

Depression, mood state, and back pain during microgravity simulated by bed rest.

OBJECTIVE: The objective of this study was to develop a ground-based model for spinal adaptation to microgravity and to study the effects of spinal adaptation on depression, mood state, and pain intensity. METHODS: We investigated back pain, mood state, and depression in six subjects, all of whom were exposed to microgravity, simulated by two forms of bed rest, for 3 days. One form consisted of bed rest with 6 degrees of head-down tilt and balanced traction, and the other consisted of horizontal bed rest. Subjects had a 2-week period of recovery between the studies. The effects of bed rest on pain intensity in the lower back, depression, and mood state were investigated. RESULTS: Subjects experienced significantly more intense lower back pain, lower hemisphere abdominal pain, headache, and leg pain during head-down tilt bed rest. They had higher scores on the Beck Depression Inventory (ie, were more depressed) and significantly lower scores on the activity scale of the Bond-Lader questionnaire. CONCLUSIONS: Bed rest with 6 degrees of head-down tilt may be a better experimental model than horizontal bed rest for inducing the pain and psychosomatic reactions experienced in microgravity. Head-down tilt with balanced traction may be a useful method to induce low back pain, mood changes, and altered self-rated activity level in bed rest studies.     

Motion compensation for interventional navigation on 3D static roadmaps based on an affine model and gating

Current cardiac interventions are performed under 2D fluoroscopy, which comes along with well-known burdens to patients and physicians, such as x-ray exposure and the use of contrast agent. Furthermore, the navigation on complex structures such as the coronaries is complicated by the use of 2D images in which the catheter position is only visible while the contrast agent is introduced. In this work, a new method is presented, which circumvents these drawbacks and enables the cardiac interventional navigation on motion-compensated 3D static roadmaps. For this, the catheter position is continuously reconstructed within a previously acquired 3D roadmap of the coronaries. The motion compensation makes use of an affine motion model for compensating the respiratory motion and compensates the motion due to cardiac contraction by gating the catheter position. In this process, only those positions which have been acquired during the rest phase of the heart are used for the reconstruction. The method necessitates the measurement of the catheter position, which is done by using a magnetic tracking system. Nevertheless, other techniques, such as image-based catheter tracking, can be applied. This motion compensation has been tested on a dynamic heart phantom. The evaluation shows that the algorithm can reconstruct the catheter position on the 3D static roadmap precisely with a residual motion of 1.0 mm and less.     

Aligning compensation with education: design and implementation of the Educational Value Unit (EVU) system in an academic internal medicine department.

The authors report the development of a new metric for distributing university funds to support faculty efforts in education in the department of internal medicine at the University of Kansas School of Medicine. In 2003, a committee defined the educational value unit (EVU), which describes and measures the specific types of educational work done by faculty members, such as core education, clinical teaching, and administration of educational programs. The specific work profile of each faculty member was delineated. A dollar value was calculated for each 0.1 EVU. The metric was prospectively applied and a faculty survey was performed to evaluate the faculty's perception of the metric. Application of the metric resulted in a decrease in university support for 34 faculty and an increase in funding for 23 faculty. Total realignment of funding was US$1.6 million, or an absolute value of US$29,072 +/- 38,320.00 in average shift of university salary support per faculty member. Survey results showed that understanding of the purpose of university funding was enhanced, and that faculty members perceived a more equitable alignment of teaching effort with funding. The EVU metric resulted in a dramatic realignment of university funding for educational efforts in the department of internal medicine. The metric was easily understood, quickly implemented, and perceived to be fair by the faculty. By aligning specific salary support with faculty's educational responsibilities, a foundation was created for applying mission-based incentive programs.     

Neural compensation for fatigue-induced changes in muscle stiffness during perturbations of elbow angle in human.

1. The contribution to muscle force regulation provided by reflex pathways was studied in the elbow flexor muscles of seven normal human subjects, with the use of voluntary fatigue to induce a deficit in the force-generating capability of these muscles. To estimate the changes in the mechanical state of the muscle and the compensatory actions taken by reflex pathways to minimize the impact of fatigue, stochastic and "step" angular perturbations were applied to the joint, and the resulting joint stiffness and electromyographic (EMG) responses were compared before and after fatigue. 2. The magnitude of contractile fatigue, induced by repeatedly lifting a weight via a pulley system, was quantified by comparing the slope of the isometric torque-EMG relationship before and after fatigue. The exercise routine was quite effective in producing severe and long-lasting fatigue, with average percentage changes in the isometric torque-EMG slope of 210-306% for biceps and 129-205% for brachioradialis, depending on the point in time examined. 3. The torque response to a rapid step stretch of the elbow joint was quite similar before and after fatigue for the time interval before reflex action (less than 20 ms after stretch onset), suggesting that intrinsic muscle stiffness for a given mean torque level was not changed by fatigue. The steady-state torque level attained after completion of the stretch was always decreased after fatigue, indicating a decrease in the reflex component of joint stiffness, but this decrease was small compared with the change in the isometric torque-EMG relationship and was accompanied by a significantly larger incremental EMG response after fatigue. This increase in incremental EMG after fatigue was found to be of reflex origin, with activation-related reflex gain changes apparently playing a significant role only at low contraction levels. 4. Torque and angle responses recorded during stochastic perturbations were used to identify elbow joint compliance impulse responses. A second-order mechanical model was fit to each impulse response, and the parameters representing joint inertia, elastic stiffness, and viscous stiffness were used to summarize changes in joint mechanical properties as the mean contraction level was varied. For a perturbation with a relatively wide bandwidth (0-25 Hz), fatigue had little or no effect on the form of the compliance impulse response, apparently because the stimulus disabled reflex force generation in elbow flexor muscles, whereas a perturbation with a more restricted bandwidth (0-10 Hz) demonstrated consistent decreases in joint stiffness after fatigue.(ABSTRACT TRUNCATED AT 400 WORDS)     

A model for flexi-bar to evaluate intervertebral disc and muscle forces in exercises

This study developed and validated a lumped parameter model for the FLEXI-BAR, a popular training instrument that provides vibration stimulation. The model which can be used in conjunction with musculoskeletal-modeling software for quantitative biomechanical analyses, consists of 3 rigid segments, 2 torsional springs, and 2 torsional dashpots. Two different sets of experiments were conducted to determine the model's key parameters including the stiffness of the springs and the damping ratio of the dashpots. In the first set of experiments, the free vibration of the FLEXI-BAR with an initial displacement at its end was considered, while in the second set, forced oscillations of the bar were studied. The properties of the mechanical elements in the lumped parameter model were derived utilizing a non-linear optimization algorithm which minimized the difference between the model's prediction and the experimental data. The results showed that the model is valid (8% error) and can be used for simulating exercises with the FLEXI-BAR for excitations in the range of the natural frequency. The model was then validated in combination with AnyBody musculoskeletal modeling software, where various lumbar disc, spinal muscles and hand muscles forces were determined during different FLEXI-BAR exercise simulations.     

Coordinated ground forces exerted by buttocks and feet are adequately programmed for weight transfer during sit-to-stand

The purpose of this study was to test the hypothesis whether weight transfer during sit-to-stand (STS) is the result of coordinated ground forces exerted by buttocks and feet before seat-off. Whole-body kinematics and three-dimensional ground forces from left and right buttock as well as from left and right foot were recorded for seven adults during STS. We defined a preparatory phase from onset of the first detectable anterior/posterior (A/P) force to seat-off (buttock forces fell to 0) and a rising phase from seat-off to the decrease of center of mass (CoM) vertical velocity to zero. STS was induced by an increase of vertical and backward directed ground forces exerted by the buttocks that significantly preceded the onset of any trunk movement. All ground forces peaked before or around the moment of seat-off, whereas all kinematic variables, except trunk forward rotation and hip flexion, peaked after seat-off, during or after the rising phase. The present study suggests that the weight transfer from sit to stand is induced by ground forces exerted by buttocks and feet before seat-off, i.e., during the preparatory phase. The buttocks generate the isometric "rising forces," e.g., the propulsive impulse for the forward acceleration of the body, while the feet apply adequate damping control before seat-off. This indicates that the rising movement is a result of these coordinated forces, targeted to match the subject's weight and support base distance between buttocks and feet. The single peaked, bell-shaped profiles peaking before seat-off, were seen beneath buttocks for the "rising drive," i.e., between the time of peak backward directed force and seat-off, as well as beneath the feet for the "damping drive," i.e., from onset to the peak of forward-directed force and for CoM A/P velocity. This suggests that both beginning and end of the weight transfer process are programmed before seat-off. The peak deceleration of A/P CoM took place shortly ( approximately 100 ms) after CoM peak velocity, resulting in a well controlled CoM deceleration before seat-off. In contrast to the view of other authors, this suggests that body equilibrium is controlled during weight transfer.     

Photocrosslinkable hyaluronic acid as an internal wetting agent in model conventional and silicone hydrogel contact lenses

Photocrosslinkable methacrylated hyaluronic acid (HA) was prepared and incorporated into model conventional and silicone hydrogel contact lenses as an internal wetting agent. The molecular weight of the HA, the degree of methacrylation as well as the amount (0.25 to 1.0 wt %) incorporated were varied. The HA-containing hydrogels were analyzed using a variety of techniques including water contact angles, equilibrium water content (EWC), and lysozyme sorption. The presence of HA could be detected in the materials using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy-attenuated total reflectance. The materials containing methacrylated HA had improved hydrophilicity and reduced lysozyme sorption. Effects of modified HA on EWC were dependent upon the materials but generally increased water uptake. Increased mobility of the HA associated with a lower molecular weight and lower degree of methacrylation was found to be more effective in improving hydrophilicity and decreasing lysozyme sorption than the less mobile HA. All results found suggest that photocrosslinkable HA has significant potential in contact lens applications.     

Impedance control and internal model use during the initial stage of adaptation to novel dynamics in humans

This study investigated the neuromuscular mechanisms underlying the initial stage of adaptation to novel dynamics. A destabilizing velocity-dependent force field (VF) was introduced for sets of three consecutive trials. Between sets a random number of 4–8 null field trials were interposed, where the VF was inactivated. This prevented subjects from learning the novel dynamics, making it possible to repeatedly recreate the initial adaptive response. We were able to investigate detailed changes in neural control between the first, second and third VF trials. We identified two feedforward control mechanisms, which were initiated on the second VF trial and resulted in a 50% reduction in the hand path error. Responses to disturbances encountered on the first VF trial were feedback in nature, i.e. reflexes and voluntary correction of errors. However, on the second VF trial, muscle activation patterns were modified in anticipation of the effects of the force field. Feedforward cocontraction of all muscles was used to increase the viscoelastic impedance of the arm. While stiffening the arm, subjects also exerted a lateral force to counteract the perturbing effect of the force field. These anticipatory actions indicate that the central nervous system responds rapidly to counteract hitherto unfamiliar disturbances by a combination of increased viscoelastic impedance and formation of a crude internal dynamics model.     

Prediction method for decreases in blood pressure during hemocatharsis therapy by arteriolar blood flow measurement

In clinical practice, the prediction of changes in blood pressure during hemocatharsis therapy depends on invasive monitoring, the physician's experience, or blood pressure measurement when patients ask for it. It is extremely difficult to predict blood pressure variation in patients under general anesthesia or with disturbance of consciousness. Therefore, the prediction of blood pressure variation during hemocatharsis therapy is an important issue. To address this issue, we invented a new noninvasive continuous blood flow monitor using arteriolar blood flow measurement by laser Doppler flowmetry. Then we examined and determined some extremely important phenomena, including the relationship between rapid blood pressure change and arteriolar blood flow, and failures of the cerebral blood flow autoregulatory mechanism, through measurements in clinical practice of hemodialysis, specific hemocatharsis therapy, and drug monitoring. The results suggest that blood pressure variation during hemocatharsis therapy is highly predictable by arteriolar blood flow measurement. Therefore, this new method for arteriolar blood flow measurement might be widely useful for patients under anesthesia, anesthesia monitoring in neonatal infants and animals (no conversation ability), as well as for hemocatharsis therapy.     

Progress toward an internal control system for fragile-X induction by 5-fluorodeoxyuridine in whole-blood cultures

We have been attempting to develop a consistently reliable internal control to assure the effectiveness of the 5-fluorodeoxyuridine (FUdR) fragile-X [fra(X)] induction system. We carried out a systematic study of whole-blood specimens cultured from 56 individuals from two different laboratories. An analysis of nearly 9,000 cells demonstrated: (1) the importance of establishing baseline levels of fragile sites in each laboratory, and (2) that a combination of common fragile sites (different for each laboratory) could serve as a consistently reliable indicator of the effectiveness of the FUdR fra(X) induction system. It was suggested that a non-FUdR culture(s) should be incorporated into a laboratory's fra(X)-screening protocol, so that if there are any doubts about the effectiveness of the FUdR system a comparison to background or spontaneously occurring fragile sites can be made within the laboratory. Repeat cultures are recommended where no increase in common fragile-site frequency is observed in the FUdR induction system, and where fra(X) was strongly suspected but not found. In addition, the necessity of using more than one fra(X) induction system in whole-blood cultures was demonstrated, including the effectiveness of an FUdR/excess thymidine double-induction system. Finally, 2 cases of apparent mosaicism for Klinefelter syndrome in fra(X) individuals were observed.