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Biomedical subjects

R B Anderson

Publications and source records attributed to R B Anderson.

At least 19 recordsLinked to original sources

DCC plays a role in navigation of forebrain axons across the ventral midbrain commissure in embryonic xenopus.

In the developing vertebrate brain, growing axons establish a scaffold of axon tracts connected across the midline via commissures. We have previously identified a population of telencephalic neurons that express NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM that is involved in axon guidance in the forebrain. These axons arise from the presumptive telencephalic nucleus, course caudally along the principal longitudinal tract of the forebrain, cross the ventral midline in the midbrain, and then project to the contralateral side of the brain. In the present study we have investigated mechanisms controlling the growth of these axons across the ventral midline of the midbrain. The axon guidance receptor DCC is expressed by the NOC-2 population of axons both within the longitudinal tract and within the ventral midbrain commissure. Disruption of DCC-dependent interactions, both in vitro and in vivo, inhibited the NOC-2 axons from crossing the ventral midbrain. Instead, these axons grew along aberrant trajectories away from the midline, suggesting that DCC-dependent interactions are important for overcoming inhibitory mechanisms within the midbrain of the embryonic vertebrate brain. Thus, coordinated responsiveness of forebrain axons to both chemostimulatory and chemorepulsive cues appears to determine whether they cross the ventral midline in the midbrain.

Animals↗

Physical Symptoms Distress Index: a sensitive tool to evaluate the impact of pharmacological agents on quality of life.

OBJECTIVES: To examine whether the degree of stress associated with adverse physical side effects correlates with overall quality of life (QOL) and compliance rates. To determine if instruments used to assess QOL can detect differences between treatments that have no known central nervous system effects. PATIENTS AND METHODS: This randomized, double-blind, parallel group study evaluated 180 to 480 mg of controlled onset, extended release (COER)-verapamil (n = 259) or 30 to 120 mg/d of nifedipine gastrointestinal therapeutic system (GITS) (n = 269) in men and women between 21 and 80 years of age with stages 1 to 3 hypertension. A battery of questions evaluating psychological well-being and a physical symptom distress index was administered after a 4-week placebo washout (baseline) and after 10 weeks of treatment or at dropout. RESULTS: Both treatments effectively lowered blood pressure, and there were no significant between-group differences in psychosocial QOL. A difference in the level of physical symptom distress was detected between treatments (P = .002; multivariate analysis of variance), with 7 significant univariate treatment effects, all favoring COER-verapamil, being noted-pedal edema, polyuria, rapid heart beat or palpitations, hives, muscle cramps, abdominal cramps, and headaches. Constipation-related distress increased significantly (P = .001) but to a similar extent with both treatments. The difference in symptom distress tended to predict compliance as there were more withdrawals in the nifedipine GITS group (n = 85) vs COER-verapamil group (n = 64) (P = .08). CONCLUSIONS: Patient-assessed physical symptom distress is a sensitive, simple technique to evaluate the effect of antihypertensive medications on QOL and tolerability, as shown by its ability to detect the improvement associated with COER-verapamil. Depending on the agents involved, the Physical Symptom Distress Index may more closely predict dropout rates than the traditional psychosocial instruments, as suggested by the lower dropout rate in the COER-verapamil group. Thus, in studying treatment effects on QOL, both the distress of physical symptoms and the impact of psychosocial factors should be evaluated.

Adult↗

Role of acetylcholinesterase in the development of axon tracts within the embryonic vertebrate brain.

In the developing vertebrate brain, acetylcholinesterase (AChE) expression coincides temporally with axon tract formation. Although AChE promotes neurite outgrowth in vitro, the role of this molecule in the development of axon tracts in vivo is unknown. To address this question, we examined the effects of the AChE inhibitor, BW284C51, on the formation of the early scaffold of axon tracts in the embryonic Xenopus brain. In exposed Xenopus brain preparations, axons elongate and establish a normal topography of axon tracts. However, when brains were exposed to BW284C51, the thickness of the major longitudinal axon tract, the tract of the post-optic commissure decreased in a dose-dependent manner. When BW284C51 was removed from the culture media axon tract development returned to normal within 5 h. These findings provide the first evidence for a non-classical role of AChE in the initial formation of axon tracts within the developing vertebrate brain.

Acetylcholinesterase↗

Neuronal pathfinding during development of the rostral brain in Xenopus.

1. The aim of the present study is to define the trajectory of growing axons as well as to characterize guidance cues mediating neuronal pathfinding in the rostral brain of embryonic Xenopus. 2. The early embryonic Xenopus brain consists of a stereotypical pattern of axon tracts arranged about orthogonal axes. This scaffold of axons is constructed around the tracts of the postoptic commissure (TPOC), a pair of longitudinal tracts that course along the ventrolateral surface of the brain. These tracts are connected across the midline by two commissures. Three short tracts join the dorsal brain to the TPOC. 3. The TPOC consists of chemically distinct subpopulations of axons defined by the expression of NOC, novel glycoforms of the neural cell adhesion molecule N-CAM. Axons expressing NOC-2 sort out in the ventral portion of the TPOC. NOC-2+ axons in the supraoptic tract appear to fasciculate with axons expressing the same cell adhesion molecule in the ventral TPOC. 4. Chondroitin sulphates modulate the growth of axons from the TPOC into the ventral tegmental commissural pathway in the rostral midbrain. 5. Unique guidance cues are responsible for neuronal pathfinding at specific points in the trajectory of growing axons in the rostral brain. We have shown that selective fasciculation mediates the turning of axons into the major longitudinal tract, while specific cues are required for axons to exit this pathway.

Animals↗

Results of in situ subtalar arthrodesis for late sequelae of calcaneus fractures.

A retrospective review was performed on all patients who had an in situ subtalar arthrodesis for painful sequelae of calcaneus fractures between 1989 and 1994. Nineteen feet were available for evaluation, with a mean follow-up of 27 months (range, 12-62 months). Lateral calcaneal wall decompression was performed in seven feet. Although loss of ankle dorsiflexion was associated with anterior ankle tenderness, loss of ankle dorsiflexion was not correlated with either talar declination angles or talar height differences. There was no correlation between American Orthopaedic Foot and Ankle Society hindfoot score and talar declination, talar height, or calcaneal width. Peroneal tendon/subfibular impingement, ankle tenderness, sural nerve injury, and patient smoking were all statistically associated with lower scores. The calcaneocuboid joint was frequently involved in the fracture but was not painful at follow-up. Late pain after a calcaneal fracture is not caused by only subtalar arthrosis. Radiographic criteria alone cannot be relied upon for surgical decision making. Careful physical evaluation should be used to determine sources of pain. Distraction arthrodesis should be considered only if findings of anterior ankle impingement are present. If sural nerve symptoms are present, a sural neurectomy may be added to the procedure. Pain localized to the plantar fat pad should be managed nonoperatively. Radiographic changes in the calcaneocuboid joint rarely require surgical intervention. Based on these results, in situ subtalar arthrodesis with lateral wall decompression is the procedure of choice in most cases of subtalar traumatic arthritis with lateral wall impingement.

Adult↗

Dorsiflexion metatarsal osteotomy for treatment of recalcitrant diabetic neuropathic ulcers.

Twenty diabetic patients underwent 22 dorsiflexion metatarsal osteotomies for treatment of chronic persistent or recurrent neuropathic forefoot ulcers. Mean duration of nonoperative treatment was 13 months. The procedure consisted of irrigation and debridement of the ulcer followed by basilar closing wedge metatarsal osteotomy performed through a dorsal approach. At follow-up, complete ulcer healing was noted in 21 cases (95%) at an average of 40 days postoperatively. Complications occurred in 15 cases (68%). The main problems encountered postoperatively were acute Charcot disease (32%) and deep wound infections (14%). Transfer lesions under adjacent metatarsal heads developed in two cases (9%). One ulcer (5%) failed to heal secondary to vascular insufficiency and eventually required a below the knee amputation after a failed revascularization attempt. Loss of screw fixation occurred in one patient (5%) but acceptable metatarsal alignment was maintained and the ulcer healed uneventfully. There were no cases of ulcer recurrence. The results of this study suggest that dorsiflexion metatarsal osteotomy is a reliable salvage procedure for the treatment of recalcitrant neuropathic forefoot ulcers that have failed an adequate trial of nonoperative treatment. This procedure is associated with a high complication rate, as would be expected in this patient population.

Adult↗

Intermediate to long-term follow-up of medial-approach dorsal cheilectomy for hallux rigidus.

Dorsal cheilectomy of the hallux metatarsophalangeal (MTP) joint through a medial approach can effectively provide long-term relief of pain and improve function in symptomatic mild-to-moderate hallux rigidus, despite progression of generalized first MTP joint arthritic degeneration and/or loss of motion. Fifty-seven patients (75 feet) with arthritis of the first MTP joint underwent dorsal cheilectomy through a medial approach for hallux rigidus failing nonoperative management. Excision of the dorsal articular surface of the first metatarsal head and dorsal osteophytes was performed through a medial approach that also allowed for plantar capsular release and removal of lateral osteophytes. Minimum follow-up was 3 years (average, 63 months; range, 37-92 months). Fifty-two patients (68 feet) returned for clinical and radiographic evaluation. American Orthopaedic Foot and Ankle Society Hallux Rating scores improved from a preoperative average of 45 to 85 points at follow-up. Average dorsiflexion improved from 19 degrees to 39 degrees, and the average range of motion improved from 34 degrees to 64 degrees. Preoperative radiographic grade of arthritic degeneration was grade I in 17 feet, grade II in 39 feet, and grade III in 12 feet; at follow-up, the radiographic grade was grade I in 2 feet, grade II in 26 feet, and grade III in 40 feet. Thirty-two feet worsened one grade, 6 feet worsened two grades, and 28 feet demonstrated no change (12 of 28 were grade III, preoperatively). A dorsal spur recurred in 21 feet, 9 of which were symptomatic. Complications included two superficial wound infections and four transient paresthesias of the hallux, all of which resolved uneventfully.

Adult↗

Clinical evaluation of the modified Brostrom-Evans procedure to restore ankle stability.

The modified Brostrom procedure has become the standard for anatomic repair of symptomatic chronic lateral instability. However, it was our perception that this local tissue repair may fail eventually, particularly in patients that are overweight, hyperflexible, or are involved in strenuous work or athletic activity. This is a retrospective review of 21 lateral ankle reconstructions (20 patients) in which the modified Brostrom technique was augmented with a portion of the peroneus brevis tendon. All patients were interviewed at an average of 29.5 months (range, 14-56 months postsurgery). Fourteen patients also agreed to be evaluated by a physical therapist. No surgical complications were identified. American Orthopaedic Foot and Ankle Society ankle-hindfoot scores averaged 98.2. There was no significant difference in passive or active range of motion of plantarflexion or dorsiflexion when compared to the contralateral ankle. However, a statistically significant loss of inversion (passive, P = 0.011; active, P = 0.018) and eversion (passive, P = 0.004; active, P = 0.007) was noted when compared to the contralateral ankle. Measurement of isometric eversion strength, using a Cybex 340 Isokinetic device, and functional testing, using a lateral lunge test, revealed no significant loss of peroneal strength. The authors conclude that chronic lateral ankle instability in the general population can be successfully managed with a modified Brostrom procedure augmented with a portion of the peroneus brevis. The procedure remains technically simple and provides a greater static restraint for inversion stress without evidence of dramatic overtightening or loss of peroneal strength.

Adult↗

Novel guidance cues during neuronal pathfinding in the early scaffold of axon tracts in the rostral brain.

A scaffold of axons consisting of a pair of longitudinal tracts and several commissures is established during early development of the vertebrate brain. We report here that NOC-2, a cell surface carbohydrate, is selectively expressed by a subpopulation of growing axons in this scaffold in Xenopus. NOC-2 is present on two glycoproteins, one of which is a novel glycoform of the neural cell adhesion molecule N-CAM. When the function of NOC-2 was perturbed using either soluble carbohydrates or anti-NOC-2 antibodies, axons expressing NOC-2 exhibited aberrant growth at specific points in their pathway. NOC-2 is the first-identified axon guidance molecule essential for development of the axon scaffold in the embryonic vertebrate brain.

Animals↗

Chondroitin sulfates modulate axon guidance in embryonic Xenopus brain.

Chondroitin sulfate proteoglycans display both inhibitory and stimulatory effects on cell adhesion and neurite outgrowth in vitro. The functional activity of these proteoglycans appears to be context specific and dependent on the presence of different chondroitin sulfate-binding molecules. Little is known about the role of chondroitin sulfate proteoglycans in the growth and guidance of axons in vivo. To address this question, we examined the effects of exogenous soluble chondroitin sulfates on the growth and guidance of axons arising from a subpopulation of neurons in the vertebrate brain which express NOC-2, a novel glycoform of the neural cell adhesion molecule N-CAM. Intact brains of stage 28 Xenopus embryos were unilaterally exposed to medium containing soluble exogenous chondroitin sulfates. When exposed to chondroitin sulfate, NOC-2(+) axons within the tract of the postoptic commissure failed to follow their normal trajectory across the ventral midline via the ventral commissure in the midbrain. Instead, these axons either stalled or grew into the dorsal midbrain or continued growing longitudinally within the ventral longitudinal tract. These findings suggest that chondroitin sulfate proteoglycans indirectly modulate the growth and guidance of a subpopulation of forebrain axons by regulating either matrix-bound or cell surface cues at specific choice points within the developing vertebrate brain.

Animals↗

Inhibitory consequences of memory selection.

When subjects select a prime from a visual display while leaving a distractor prime unselected, response time (RT) or response accuracy to a subsequent probe may be impeded if the distractor prime and probe are identical, or if they are related to one another. This phenomenon, negative priming (NP), has obvious implications for understanding perceptual selection. However, it is not known whether NP results from other kinds of selection processes. The present studies were designed to investigate whether NP occurs when primes are selected from working memory rather than from a visual display. In the two experiments, the subjects memorized two primes, selected one prime for further processing, and classified the contents of a probe display. Significant NP occurred in both Experiments. In Experiment 2, however, NP occurred only under easy-selection conditions; the effect was reversed under difficult-selection conditions. The findings indicate a role for NP in memory processing, but contrast with the results from perceptual selection studies showing greater NP under difficult-selection than under easy-selection conditions. The present finding suggests a complex and perhaps strategy-dependent relationship between memory selection difficulty and NP.

Analysis of Variance↗

Autogenous bone grafting of hallux sesamoid nonunions.

We first performed autogenous bone grafting for lesions of the hallux sesamoid in 1984. During the next 9 years, 21 patients (11 men and 10 women with an average age of 34 and 32 years, respectively) underwent this surgical procedure for symptomatic tibial hallux sesamoid non-unions. Successful bony union was achieved in all but two patients. The majority of patients obtained concomitant relief of preoperative symptomatology and returned to their preinjury level of activity. We believe that this procedure serves as an alternative to hallux sesamoid excision in selected cases.

Adult↗

Artifactual power curves in forgetting.

Recent studies of the mathematical relationship between time and forgetting suggest that it is a power function rather than an exponential function, a finding that has important theoretical consequences. Through computational analysis and reanalyses of published data, we demonstrate that arithmetic averaging of exponential curves can produce an artifactual power curve, particularly when there are large and systematic differences among the slopes of the component curves. A series of simulations showed that the amount of power artifact is small when the slopes of the component curves are normally or rectangularly distributed and when the performance measure is noise free. However, the simulations also showed that the artifact can be quite large, depending on the shape of the noise distribution and restrictions in the performance range. We conclude that claims concerning the form of memory functions should consider whether the data are likely to contain artifact caused by averaging or by the presence of range-restricted noise.

Artifacts↗

Need probability affects retention: a direct demonstration.

Recent memory theory has emphasized the concept of need probability--that is, the probability that a given piece of learned information will be tested at some point in the future. It has been proposed that, in real-world situations, need probability declines over time and that the memory-loss rate is calibrated to match the progressive reduction in need probability (J.R. Anderson & Schooler, 1991). The present experiments were designed to examine the influence of the slope of the need-probability curve on the slope of the retention curve. On each of several trials, subjects memorized a list of digits, then retained the digits in memory for 1, 2, 4, 8, or 16 sec. Some trials ended with a recall test; other trials ended with the message, "no test." In Experiment 1, the likelihood of encountering a memory test (i.e., the need probability) was made to either increase or decrease as the retention interval increased; in Experiment 2, need probability either was flat (invariant across retention intervals) or decreased as the retention interval increased. The results indicated that the shape of the need-probability curve influenced the slope of the retention curve (Experiment 1) and that the effect became larger as the experimental session progressed (Experiment 2). The findings support the notion that memory adapts to need probabilities and that the rate of forgetting is influenced by the slope of the need-probability curve. In addition, all of the forgetting curves approximated a power function, suggesting that need probability influences the slope but not the form of forgetting.

Educational Measurement↗

Expression of a novel N-CAM glycoform (NOC-1) on axon tracts in embryonic Xenopus brain.

The aim of the present study was to characterise the expression pattern of a novel N-CAM glycoform, called NOC-1, within axon tracts of the developing Xenopus brain. Double-label immunostaining of wholemount embryonic brains revealed that only a subpopulation of axons express NOC-1. Axons in the supra-optic tract (SOT) express NOC-1 and course ventrally from the presumptive telencephalon to join the tract of the post-optic commissure (TPOC), the principal longitudinal tract of the forebrain. NOC-1 was also expressed by axons that form discrete fascicles in the ventral portion of the TPOC. Growth cones in the SOT appeared to only turn caudally upon contacting the NOC-1 expressing axons in the ventral region of the TPOC. Thus, all NOC-1 expressing axons within the TPOC follow a common ventral pathway. These observations demonstrate that there is selective partitioning of axons which express a novel N-CAM glycoform within the developing Xenopus forebrain. Moreover, these results indicate that the SOT-TPOC junction is an important choice point for ventrally growing SOT axons and that selective interactions occur between subpopulations of axons expressing NOC-1 in the SOT and TPOC.

Animals↗