Peritonitis caused by Blastomyces dermatitidis in a kidney transplant recipient: case report and literature review.

Blastomyces dermatitidis is a dimorphic fungus endemic to the midwestern, south-central, and southeastern United States known to cause disseminated infection in immunocompromised individuals. We report a case of B. dermatitidis peritonitis in a renal allograft recipient with new-onset ascites and cytomegalovirus encephalitis. Peritoneal blastomycosis is a rare clinical entity and, to our knowledge, this patient represents the first known case of peritoneal blastomycosis in a solid organ transplant recipient. We review the clinical characteristics of B. dermatitidis peritonitis as well as the literature on fungal peritonitis with emphasis on dimorphic fungal pathogens. Clinical features suggestive of fungal peritonitis include new-onset ascites, abdominal pain, and fevers, especially with antecedent or concomitant pneumonia. A high index of clinical suspicion, along with the use of culture and non-culture diagnostics, is needed for early diagnosis and prompt initiation of therapy.

Delayed influence of stretch-shortening cycle fatigue on large ankle joint position coded with static positional signals.

This study examines the static position sense from the ankle joint following a unilateral exhaustive stretch-shortening cycle (SSC)-type exercise involving mostly the triceps surae muscle group. Fatigue effects were quantified within the exercised and non-exercised leg through a maximal isometric voluntary plantarflexion test (MVC) performed immediately before (Pre) and after the SSC exercise, and repeated 2 (D2) and 8 (D8) days later. The static position sense test consisted in active reproductions with the non-exercised ankle of two target dorsiflexed positions (small and large) previously maintained with either the non-exercised (control procedure) or the exercised ankle (fatigue procedure). This test was carried out at Pre, D2, and D8. At D2, the MVC test revealed significant decreases in voluntary soleus muscle activity and peak plantarflexion force. The position sense test showed no error in reproduction accuracy in the control procedure. In contrast, the fatigue procedure revealed an overestimation of the large dorsiflexed position, only, with an associated increase of the agonist tibialis muscle activity. In agreement with the antagonist (stretched) muscle influence on the position sense, this overestimation is mostly attributed to potential SSC fatigue effects on ascending proprioceptive afferents issued from the exercised/inflamed antagonist muscles.

Judging beforehand the possibility of passing under obstacles without motion: the influence of egocentric and geocentric frames of reference.

Previous studies have shown that the perception of the earth-based visual horizon, also named Gravity Referenced Eye Level (GREL), is modified by body tilt around a trans-ocular axis. Here, we investigated whether estimates of the elevation of a luminous horizontal line presented on a screen in otherwise darkness and estimates of the possibility of passing under are identically related to body tilt in absence of motion. Results showed that subjects overestimated the elevation of the projected line, whatever their body orientation. In the same way, subjects also overestimated their capacity of passing under the line. Both estimates appeared as a linear function of body tilt, that is, forward body tilt yielded increased overestimations, and backward body tilt yielded decreased overestimations. More strikingly, the linear effect of body tilt upon these estimates is comparable to that previously observed for direct GREL judgements. Overall, these data strongly suggest that the perception of the elevation of a visible obstacle and the perception of the ability of passing under in otherwise darkness shared common processes which are intimately linked to the GREL perception. The effect of body tilt upon these perceptions may illustrate an egocentric influence upon the semi-geocentric frame of reference required to perform the task. Possible interactions between egocentric and geocentric frames of reference are discussed.

Changes in illusory ankle movements induced by tendon vibrations during the delayed recovery phase of stretch-shortening cycle fatigue: an indirect study of muscle spindle sensitivity modifications.

This study examined the perceived movement velocity induced by tendon vibrations during the delayed recovery phase of a stretch-shortening cycle (SSC)-type exercise characterized by 2 to 4 days of neuromuscular and proprioceptive impairments. Seven subjects performed until exhaustion series of unilateral rebounds involving mostly the triceps surae muscle group. Fatigue effects were quantified for the exercised and non-exercised legs through muscle soreness and maximal voluntary plantarflexion test (MVC) performed immediately before (PRE) and after the SSC exercise, and repeated 2 days later (D2). At PRE and D2, mechanical vibrations at 40, 60, 80, 100, and 120 Hz were applied to distal tendons of the exercised ankle. For each vibration, the subjects had to reproduce the perceived movement velocity with the non-exercised ankle. According to previous studies, the sole exercised leg was characterized by a D2 peak of muscle soreness associated, in the MVC test, with significant decreases in maximal force and mean soleus muscle activity. As compared to the PRE test and in all subjects, the vibrations applied at D2 to the tendon of the fatigued ankle extensor muscles led to significant decreases in the perceived movement velocity at 80 and 100 Hz, but to an increased one at 40 Hz. In contrast, vibrations applied to the tendon of the non-fatigued ankle flexor muscle did not result in any significant change. These results suggest that the delayed recovery phase of SSC fatigue is characterized by changes in muscle proprioception, which may partly result from a decreased sensitivity of the primary endings.

Development and application of a green fluorescent protein sentinel system for identification of RNA interference in Blastomyces dermatitidis illuminates the role of septin in morphogenesis and sporulation.

A high-throughput strategy for testing gene function would accelerate progress in our understanding of disease pathogenesis for the dimorphic fungus Blastomyces dermatitidis, whose genome is being completed. We developed a green fluorescent protein (GFP) sentinel system of gene silencing to rapidly study genes of unknown function. Using Gateway technology to efficiently generate RNA interference plasmids, we cloned a target gene, "X," next to GFP to create one hairpin to knock down the expression of both genes so that diminished GFP reports target gene expression. To test this approach in B. dermatitidis, we first used LACZ and the virulence gene BAD1 as targets. The level of GFP reliably reported interference of their expression, leading to rapid detection of gene-silenced transformants. We next investigated a previously unstudied gene encoding septin and explored its possible role in morphogenesis and sporulation. A CDC11 septin homolog in B. dermatitidis localized to the neck of budding yeast cells. CDC11-silenced transformants identified with the sentinel system grew slowly as flat or rough colonies on agar. Microscopically, they formed ballooned, distorted yeast cells that failed to bud, and they sporulated poorly as mold. Hence, this GFP sentinel system enables rapid detection of gene silencing and has revealed a pronounced role for septin in morphogenesis, budding, and sporulation of B. dermatitidis.

Blastomycosis in solid organ transplant recipients.

BACKGROUND: Blastomyces dermatitidis, the etiologic agent of blastomycosis, causes severe disease and substantial mortality in those immunocompromised by acquired immunodeficiency syndrome or malignancy. In solid organ transplant recipients, the epidemiology, clinical features, and outcomes have not been fully described. METHODS: We conducted a retrospective case-series at the University of Wisconsin Hospital and Clinics. Case patients were solid organ transplant recipients with blastomycosis. RESULTS: From 1986 to 2004, we identified 11 cases of post-transplant blastomycosis with 64% occurring between 2000 and 2004. Onset of infection occurred a median of 26 months post transplantation with near equal distribution before and after the first year of transplantation. Rejection did not precede any case of post-transplant blastomycosis. Opportunistic co-infections were common, occurring in 36% of patients. Pneumonia was the most common clinical presentation and was frequently complicated by acute respiratory distress syndrome (ARDS). Extrapulmonary disease predominantly involved the skin and spared the central nervous system. The overall mortality rate was 36%; however, this increased to 67% in those with ARDS. None of the surviving patients relapsed or received routine secondary antifungal prophylaxis. CONCLUSION: Blastomycosis is an uncommon infection following solid organ transplantation that is frequently complicated by ARDS, dissemination, and opportunistic co-infection. After cure, post-transplant blastomycosis may not require lifelong antifungal suppression.

Vision of the hand prior to movement onset allows full motor adaptation to a multi-force environment.

In everyday life, because of unexpected mechanical perturbation applied to the hand or to the whole body, hand movements may become suddenly inaccurate. With prolonged exposure to the perturbation, trajectories slowly recover their normal accuracy, which is the mark of motor adaptation. However, full development of this adaptive process in complete darkness has been recently challenged in a multi-force environment. Here, we report on the effectiveness of static hand position information as specified through vision prior to movement onset on the adaptative changes, over trials, of pointing movements performed in a gravitoinertial force field. For this, subjects seated off-center on a platform rotating at constant velocity, were either confined to complete darkness (No Vision Session, NV) or provided with vision of the hand resting on the starting position prior to movement onset (Hand Vision Prior to Movement Session, HVPM). Overall, our results showed that adaptation to the centrifugal force was very rapid, and allowed subjects to demonstrate appropriate motor control as early as of the very first trials performed during the rotation period, even in the NV condition. They also showed that the integration by the Central Nervous System (CNS) of visual and proprioceptive information prior to the execution of a reaching movement allows subjects to reach full motor adaptation in a multi-force environment. Furthermore, our data confirm the existence of differentiated motor adaptive mechanisms for centrifugal and Coriolis forces. Adaptation to the former may fully develop on the basis of an a priori coding of the characteristics of the background force level even without visual information, while the latter needs visual cues about hand position prior to movement onset to take place.

Subtherapeutic ocular penetration of caspofungin and associated treatment failure in Candida albicans endophthalmitis.

Candida endophthalmitis represents the most serious ocular complication of candidemia. The pharmacokinetics and pharmacodynamics of fluconazole, amphotericin B, and flucytosine are fairly well established in endophthalmitis therapy. There remains a paucity of clinical data regarding the utility of new antimycotic agents in the treatment of fungal chorioretinitis and endophthalmitis. We report a case of clinical failure of caspofungin in the management of Candida albicans endophthalmitis associated with poor vitreous penetration.

Accuracy of spatial localization depending on head posture in a perturbed gravitoinertial force field.

Spatial orientation is crucial when subjects have to accurately reach memorized visual targets. In previous studies modified gravitoinertial force fields were used to affect the accuracy of pointing movements in complete darkness without visual feedback of the moving limb. Target mislocalization was put forward as one hypothesis to explain this decrease in accuracy of pointing movements. The aim of this study was to test this hypothesis by determining the accuracy of spatial localization of memorized visual targets in a perturbed gravitoinertial force field. As head orientation is involved in localization tasks and carrying relevant sensory systems (visual, vestibular and neck muscle proprioceptive), we also tested the effect of head posture on the accuracy of localization. Subjects (n=10) were seated off-axis on a rotating platform (120 degrees s(-1)) in complete darkness with the head fixed (head-fixed session) or free to move (head-free session). They were required to report verbally the egocentric spatial localization of visual memorized targets. They gave the perceived target location in direction (i.e. left or right) and in amplitude (in centimeters) relative to the direction they thought to be straight ahead. Results showed that the accuracy of visual localization decreased when subjects were exposed to inertial forces. Moreover, subjects localized the memorized visual targets more to the right than their actual position, that was in the direction of the inertial forces. With further analysis, it appeared that this shift of localization was concomitant with a shift of the visual straight ahead (VSA) in the opposite direction. Thus, the modified gravitoinertial force field led to a modification in the orientation of the egocentric reference frame. Furthermore, this shift of localization increased when the head was free to move while the head was tilted in roll toward the center of rotation of the platform and turned in yaw in the same direction. It is concluded that the orientation of the egocentric reference frame was influenced by the gravitoinertial vector.

Galvanic vestibular stimulation in humans produces online arm movement deviations when reaching towards memorized visual targets.

Using galvanic vestibular stimulation (GVS), we tested whether a change in vestibular input at the onset of goal-directed arm movements induces deviations in arm trajectory. Eight head-fixed standing subjects were instructed to reach for memorized visual targets in complete darkness. In half of the trials, randomly-selected, a 3 mA bipolar binaural galvanic stimulation of randomly alternating polarity was triggered by the movement onset. Results revealed significant GVS-induced directional shifts of reaching movements towards the anode side. The earliest significant deviations of hand path occurred 240 ms after stimulation onset. The likely goal of these online deviations of arm trajectory was to compensate for a vestibular-evoked apparent change in the spatial relationship between the target and the hand.

Accuracy level of pointing movements performed during slow passive whole-body rotations.

Seated observers requested to detect low-velocity passive rotations show a high motion-detection threshold. However, when standing on a slowly rotating platform, their equilibrium is preserved, suggesting that cognitive sensing and sensorimotor reactions do not share the same central processes. The present experiments investigated the ability of observers seated on a slowly rotating chair in total darkness to indicate with their hand the position of briefly flashed targets (Experiment 1) and to indicate the subjective horizon with an outstretched arm (Experiment 2) or with a target driven by a joystick (Experiment 3). The overall hypothesis stated that egocentric coding of the position of a target should not be affected by sensing or not-sensing body rotation (Experiment 1), while geocentric positioning may (Experiments 2 and 3). Our data partially supported the hypothesis. Subjects pointed accurately to the memorized targets (Experiment 1), whereas misperception of body orientation was a source of inaccuracy for actions referred to a geocentric frame (Experiments 2 and 3). More interestingly, subjects' perceptions changed as a single, smooth, and monotonic function of tilt, independent of whether the perception of body orientation was present or not.

Weight estimation in a "deafferented" man and in control subjects: are judgements influenced by peripheral or central signals?

It is not yet certain which sources of information are most important in judging the weight of a held object. In order to study this question further, a "deafferented" man and five controls flexed their wrist to lift a container weighing 1,000 g. Direct vision of the arm and weight was denied; the container's vertical position was displayed to the subjects on an oscilloscope at the start of each trial and, then, in most experimental conditions, this display was removed. The weight was then either gradually increased or decreased over 20 s or left unchanged, on a pseudorandom basis. A verbal judgement of its change was required at the end of each trial, lasting 20 or 40 s. Under these conditions, the "deafferented" subject was unable to correctly judge the weight changes (38% accuracy, n.s. chi2, compared with 77% in control subjects), and even the control subjects, when exposed to muscle vibration, made many errors (54% accuracy). However, in many trials, including those in which the weight was unchanged, the vertical height of the container was not held constant by the subjects, but drifted up or down (mean absolute drift: approximately 2 cm). Hence, the change in muscular activation or stiffness could be estimated by the observers in the majority of trials. This allowed the verbal judgements of both the "deafferented" man and of control subjects undergoing muscle vibration to be correlated with the muscle activation produced, independent of the actual weight being tested. Post-hoc predictions of controls' responses during vibration, based on the direction of the change in muscle activity which these drifts in position implied, were 77% and 66% accurate for +/-750 g and +/-375 g tasks and 73% accurate for forearm-vibration trials (P<0.0001, chi2). Predictions of the "deafferented" subject's responses were 64% accurate (P=0.0002, chi2), even though his own responses were at a chance level with respect to the actual weight change. The judgements made by these subjects might have been based upon a peripheral sensory input, as small afferent fibres are still present in the "deafferented" man and vibration only partly blocked sensory function in the control subjects. Care was taken to minimise all other possible cues to the weight changes, e.g. vestibular, thermal, pressure or pain cues. However, peripheral inputs may not be the only signals used in the subjects' perceptual judgements. They might, instead, be based upon a centrally originating, but illusory changing sense of body position or, possibly, a changing sense of effort. In both cases, a perceived discordance between voluntary muscle activation and body image could underlie the subjects' responses. Our data do not yet allow us to distinguish between these alternative peripheral and central hypotheses, but do highlight the need to include perceptions of body position and motion into judgements of force control.

The role of proprioception and attention in a visuomotor adaptation task.

The role of proprioception in the control and adaptation of visuomotor relationships is still unclear. We have studied a deafferented subject, IW, and control subjects in a task in which they used single joint elbow extension to move to a visual target, with visual feedback of the terminal position provided by a cursor displayed in the plane of their movements. We report the differences in movement accuracy between the deafferented subject and controls in the normal task and when challenged with a cognitive load, counting backwards. All subjects were less accurate when counting; this was a small effect for the controls (<10% change) but much greater for the deafferented subject (>60% change). We also examined changes in movement kinematics when the instructed amplitude was altered via a changed gain between final arm position and presentation of the feedback cursor. The deafferented subject maintained temporal movement parameters stable and altered amplitude by scaling force (i.e. changed peak velocity), whereas the controls scaled both movement velocity and duration. Finally, we compared the subjects' adaptation of movement amplitude after a period of exposure to the changed visuomotor gain. The deafferented subject was able to adapt, but his adaptation was severely impaired by the counting task. These results suggest that proprioception is not an absolute requirement for adaptation to occur. Instead, proprioception has a more subtle role to play in the adjustment to visuomotor perturbations. It has an important role in the control of reaching movements, while in the absence of proprioception, attention appears necessary to monitor movements.

Does the oculo-manual co-ordination control system use an internal model of the arm dynamics?

The hypothesis that during self-moved target tracking, the eye-arm co-ordination control system uses an internal model of the arm dynamics was tested. The contribution of arm proprioception to this model was also assessed. Subjects (nine healthy adults and one deafferented subject) were requested to make forearm movements and visually track an arm-driven target. Unexpected changes in mechanical properties of the manipulandum were used to modify the dynamical conditions of arm movement. The smooth pursuit gain (SPG) was computed before and during the perturbation. Results showed a decrease of SPG during perturbation in control subjects only. We propose that an internal model of the arm dynamics may be used to co-ordinate eye and arm movements, and arm proprioception may contribute to this internal model.

Updating visual space during passive and voluntary head-in-space movements.

The accuracy of our spatially oriented behaviors largely depends on the precision of monitoring the change in body position with respect to space during self-motion. We investigated observers' capacity to determine, before and after head rotations about the yaw axis, the position of a memorized earth-fixed visual target positioned 21 degrees laterally. The subjects (n=6) showed small errors (mean=-0.6 degrees) and little variability (mean=0.9 degrees) in determining the position of an extinguished visual-target position when the head (and gaze) remained in a straight-ahead position. This accuracy was preserved when subjects voluntary rotated the head by various magnitudes in the direction of the memorized visual target (head rotations ranged between 5 degrees and 60 degrees). However, when the chair on which the subjects were seated was unexpectedly rotated about the yaw axis in the direction of the target (chair rotations ranged between 6 degrees and 36 degrees ) during the head-on-trunk rotations, the performance was markedly decreased, both in terms of spatial precision (mean error=5.6 degrees ) and variability (mean=5.7 degrees). A control experiment showed that the prior knowledge of chair rotation occurrence had no effect on the perceived target position after head-trunk movements. Updating an earth-fixed target position during head-on-trunk rotations could be achieved through both cervical and vestibular signals processing, but, in the present experiment, the vestibular output was the only signal that had the potentiality to contribute to accurate coding of the target position after simultaneous head and trunk movements. Our results therefore suggest that the vestibular output is a noisy signal for the central nervous signal to update the visual space during head-in-space motion.

The role of ocular muscle proprioception during modifications in smooth pursuit output.

The output of the smooth pursuit (SP) system can be increased by adding a portion of the recorded eye motion onto target motion, producing a situation analogous to that occurring with weakened ocular muscles. This change is most likely the result of alterations in the signals that code eye and target motion. We have assessed the contribution of one such signal, that arising from ocular proprioception, to the modification process during monocular SP by preventing the motion of the non-viewing eye with a suction scleral lens. The large increases normally observed for SP velocity following the modification period were substantially reduced under these conditions. Similar alterations were also observed in a manual tracking task. These results demonstrate that ocular proprioceptive signals serve to stabilize the output of the SP system following perturbations, via the recoding of eye and target motion.

Visual object localization through vestibular and neck inputs. 2: Updating off-mid-sagittal-plane target positions.

The vestibular signal plays a significant role in sensing changes in head orientation during rotations and in determining the magnitude of the rotations, but has only minor contributions in updating the internal representation of object positions with respect to the body after body rotations. The small contribution of the vestibular signal in egocentric object localization was evidenced in experiments in which the subjects reported the remembered position of eccentric earth-fixed targets after passive body rotations. The experiment reported here tested whether motor systems, such as the oculomotor system, make use of vestibular signals to generate accurate goal-directed motor responses toward a target whose position needs to be updated with respect to the body during and after whole-body rotations. The results showed that although subjects can produce saccadic eye movements of about the same magnitude as passive whole-body rotations (as previously reported by a number of researchers), they failed to generate accurate saccades toward the position of an extinguished peripheral visual target after the rotation. Overall, these results combined with those found in the literature suggest different central processes for determining changes in body orientation in complete darkness and for updating a target position with respect to the body during and after body rotations.

Role of arm proprioception in calibrating the arm-eye temporal coordination.

When subjects track with the eyes an arm-attached target, eye latency is shorter than when tracking an external target. This improved synchrony could result from either a common command addressed to the two systems or from an influence of the arm command on eye motion initiation. According to the first hypothesis, the eyes should start moving long before the arm, because of the difference in dynamics. We recorded arm and eye motion together with biceps muscle activity in controls and a deafferented subject. Data support the second hypothesis. Moreover, the deafferented subject showed a lesser correlation between arm and eye motions than controls, suggesting a role for arm proprioception in the calibration of the temporal relationship between arm and eye movements.

Self-moved target eye tracking in control and deafferented subjects: roles of arm motor command and proprioception in arm-eye coordination.

1. When a visual target is moved by the subject's hand (self-moved target tracking), smooth pursuit (SP) characteristics differ from eye-alone tracking: SP latency is shorter and maximal eye velocity is higher in self-moved target tracking than in eye-alone tracking. The aim of this study was to determine which signals (motor command and/or proprioception) generated during arm motion are responsible for the decreased time interval between arm and eye motion onsets in self-moved target tracking. 2. Six control subjects tracked a visual target whose motion was generated by active or passive movements of the observer's arm in order to determine the role played by arm proprioception in the arm-eye coordination. In a second experiment, the participation of two subjects suffering complete loss of proprioception allowed us to assess the contribution of arm motor command signals. 3. In control subjects, passive movement of the arm led to eye latencies significantly longer (130 ms) than when the arm was actively self-moved (-5 ms:negative values meaning that the eyes actually started to move before the target) but slightly shorter than in eye-alone tracking (150 ms). These observations indicate that active movement of the arm is necessary to trigger short-latency SP of self-moved targets. 4. Despite the lack of proprioceptive information about arm motion, the two deafferented subjects produced early SP (-8 ms on average) when they actively moved their arms. In this respect they did not differ from control subjects. Active control of the arm is thus sufficient to trigger short-latency SP. However, in contrast with control subjects, in deafferented subjects SP gain declined with increasing target motion frequency more rapidly in self-moved target tracking than in eye-alone tracking. 5. The deafferented subjects also tracked a self-moved target while the relationship between arm and target motions was altered either by introducing a delay between arm motion and target motion or by reversing target motion relative to arm motion. As with control subjects, delayed target motion did not affect SP latency. Furthermore, the deafferented subjects adapted to the reversed arm-target relationship faster than control subjects. 6. The results suggest that arm motor command is necessary for the eye-to-arm motion onset synchronization, because eye tracking of the passively moved arm was performed by control subjects with a latency comparable with that of eye-alone tracking of an external target. On the other hand, as evidenced by the data from the deafferented subjects, afferent information does not appear to be necessary for reducing the time between arm motion and SP onsets. However, afferent information appears to contribute to the parametric adjustment between arm motor command and visual information about arm motion.

The relative contribution of retinal and extraretinal signals in determining the accuracy of reaching movements in normal subjects and a deafferented patient.

This experiment investigated the relative extent to which different signals from the visuo-oculomotor system are used to improve accuracy of arm movements. Different visuo-oculomotor conditions were used to produce various retinal and extraretinal signals leading to a similar target amplitude: (a) fixating a central target while pointing to a peripheral visual target, (b) tracking a target through smooth pursuit movement and then pointing to the target when its excursion ceased, and (c) pointing to a target reached previously by a saccadic eye movement. The experiment was performed with a deafferented subject and control subjects. For the deafferented patient, the absence of proprioception prevented any comparison between internal representations of target and limb (through proprioception) positions during the arm movement. The deafferented patient's endpoint therefore provided a good estimate of the accuracy of the target coordinates used by the arm motor system. The deafferented subject showed relatively good accuracy by producing a saccade prior to the pointing, but large overshooting in the fixation condition and undershooting in the pursuit condition. The results suggest that the deafferented subject does use oculomotor signals to program arm movement and that signals associated with fast movements of the eyes are better for pointing accuracy than slow ramp movements. The inaccuracy of the deafferented subject when no eye movement is allowed (the condition in which the controls were the most accurate) suggests that, in this condition, a proprioceptive map is involved in which both the target and the arm are represented.