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Biomedical subjects

John Stein

Publications and source records attributed to John Stein.

At least 19 recordsLinked to original sources

Involvement of human basal ganglia in offline feedback control of voluntary movement.

Practice makes perfect, but the neural substrates of trial-to-trial learning in motor tasks remain unclear. There is some evidence that the basal ganglia process feedback-related information to modify learning in essentially cognitive tasks , but the evidence that these key motor structures are involved in offline feedback-related improvement of performance in motor tasks is paradoxically limited. Lesion studies in adult zebra finches suggest that the avian basal ganglia are involved in the transmission or production of an error signal during song . However, patients with Huntington's disease, in which there is prominent basal ganglia dysfunction, are not impaired in error-dependent modulation of future trial performance . By directly recording from the subthalamic nucleus in patients with Parkinson's disease, we demonstrate that this nucleus processes error in trial performance at short latency. Local evoked activity is greatest in response to smallest errors and influences the programming of subsequent movements. Accordingly, motor parameters are least likely to change after the greatest evoked responses so that accurately performed trials tend to precede other accurate trials. This relationship is disrupted by electrical stimulation of the nucleus at high frequency. Thus, the human subthalamic nucleus is involved in feedback-based learning.

Aged↗

Performance characteristics of clinical diagnosis, a clinical decision rule, and a rapid influenza test in the detection of influenza infection in a community sample of adults.

STUDY OBJECTIVE: The accurate diagnosis of influenza remains a diagnostic dilemma. We examine the performance of various strategies for diagnosing influenza infection in an unselected sample of adults during influenza season. METHODS: Consecutive adults presenting to a university emergency department or urgent care clinic between January and March 2002 with acute respiratory complaints were eligible for this prospective observational study. The performance of clinician judgment, a rapid influenza test, and a clinical prediction rule in predicting influenza infection was evaluated using referent standard of reverse transcriptase polymerase chain reaction. Statistical significance was assessed using McNemar's test of proportions. RESULTS: Fifty-three of 258 (21%) patients had a positive influenza reverse transcriptase polymerase chain reaction test. Overall, clinician judgment showed sensitivity of 29% (95% confidence interval [CI] 18% to 43%) and specificity of 92% (95% CI 87% to 95%). The rapid influenza test showed a sensitivity of 33% (95% CI 22% to 47%) and specificity of 98% (95% CI 96% to 99%). The clinical prediction rule showed a sensitivity of 40% (95% CI 27% to 54%) and specificity of 92% (95% CI 87% to 95%). Clinician judgment when patients presented within 48 hours showed a sensitivity of 67% (95% CI 39% to 86%) and specificity of 96% (95% CI 81% to 99%). Neither the rapid influenza test (P=.10) nor the clinical prediction rule (P=.42) was superior to clinician judgment alone in the diagnosis of influenza. CONCLUSION: The suggestion that a clinical decision rule or a rapid influenza test is better than clinical judgment alone for the diagnosis of influenza in an unselected patient population is not supported by this study.

Adolescent↗

Deep brain stimulation for generalised dystonia and spasmodic torticollis.

Dystonia appears distinct from the other tremulous disorders in that improvement following deep brain stimulation frequently appears in a delayed and progressive manner. The rate of this improvement and the point at which no further progress can be expected are presently unknown. The establishment of these parameters is important in the provision of accurate and relevant prognostic information to these patients, their carers, and their treating physicians. We studied 12 consecutive patients with generalised dystonia (n=6) and spasmodic torticollis (n=6) who underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed up for a minimum of 2 years postoperatively. Standard rating scales were used to quantify their neurological improvement. Both groups experienced a statistically significant improvement in their rating scores at both one and two years following surgery. At 2 years follow-up, the spasmodic torticollis group exhibited a 59% improvement in their total Toronto Western Spasmodic Torticoilis Rating Scale (TWSTRS) rating score and the generalised dystonia group attained a 46% improvement in their overall Burke, Fahn and Marsden Dystonia Rating Scale (BFMDRS) evaluation. Ninety-five percent of the final improvement was attained by 6.4 months in the generalised dystonia group and by 6.6 months in those with spasmodic torticollis. There was no significant improvement after one year postoperatively. These findings add further support to GPi DBS as an effective treatment for generalised dystonia and spasmodic torticollis, and furnish important information as to the expected rate of improvement and the point at which no further gains can be reasonably anticipated.

Adolescent↗

Effect of GPi DBS on functional imaging of the brain in dystonia.

Five patients with idiopathic dystonic conditions, treated successfully with deep brain stimulation (DBS) of the globus pallidus internus (GPi), were studied using single-photon emission tomography (SPET) in order to evaluate brain perfusion in the presence and absence of DBS. Comparison was made between the "on" and "off" DBS scans on an individual basis and also as part of a group analysis. Whilst the individual data suggested great regional variation in cerebral perfusion between individuals, the results of the group analysis revealed several topographically similar areas of the brain where relative hyperperfusion in the absence of DBS was common to all patients. Based on these results we postulate on possible mechanisms for this phenomenon.

Adult↗

Thalamotomy versus thalamic stimulation for multiple sclerosis tremor.

Disabling intractable tremor occurs frequently in patients with multiple sclerosis (MS). There is currently no effective medical treatment available, and the results of surgical intervention have been variable. Thalamotomy has been the mainstay of neurosurgical therapy for intractable MS tremor, however the popularisation of deep brain stimulation (DBS) has led to the adoption of chronic thalamic stimulation in an attempt to ameliorate this condition. With the goal of examining the relative efficacy and adverse effects of these two surgical strategies, we studied twenty carefully selected patients with intractable MS tremor. Thalamotomy was performed in 10 patients, with chronic DBS administered to the remaining 10. Both thalamotomy and thalamic stimulation produced improvements in postural and intention tremor. The mean improvement in postural tremor at 16.2 months following surgery was 78%, compared with a 64% improvement after thalamic stimulation (14.6 month follow-up) (P > 0.05). Intention tremor improved by 72% in the group undergoing thalamotomy, a significantly larger gain than the 36% tremor reduction following DBS (P < 0.05). Early postoperative complications were common in both groups. Permanent complications related to surgery occurred in four patients overall. Following thalamotomy, long-term adverse effects were observed in three patients (30%), and comprised hemiparesis and seizures. Only one patient in the thalamic stimulation group experienced a permanent deficit (monoparesis). We conclude that thalamotomy is a more efficacious surgical treatment for intractable MS tremor, however the higher incidence of persistent neurological deficits in patients receiving lesional surgery may support the use of DBS as the preferred surgical strategy.

Adult↗

Connectivity of the human periventricular-periaqueductal gray region.

OBJECT: The periventricular gray (PVG) zone and its continuation, the periaqueductal gray (PAG) substance, have been targets for deep brain stimulation (DBS) in the alleviation of intractable pain for longer than two decades. Nevertheless, the anatomical connectivity of this region has been fairly poorly defined. The effects of DBS in this region are probably related to the release of endogenous endorphins, but until the connectivity of this region is better understood the mechanisms will remain unclear. METHODS: Diffusion tractography was used to trace the pathways of the PVG-PAG region in seven healthy human volunteers. Images were acquired with the aid of a 1.5-tesla magnetic resonance imaging system. The region of interest was located just lateral to the posterior commissure and extended caudally to the level of the superior colliculus. Probabilistic diffusion tractography was performed from each voxel in each patient's PVG-PAG region. The PVG-PAG region was found to yield descending projections to the spinal cord and cerebellum. Ascending projections to the thalamus and frontal lobes were also observed. CONCLUSIONS: These findings suggest that the PVG-PAG region may modulate pain by two mechanisms: one involving the antinociceptive system in the spinal cord and the other involving influences on the central pain network.

Afferent Pathways↗

Magnocellular mediated visual-spatial attention and reading ability.

This study explores the relationship between attentional processing mediated by visual magnocellular (MC) processing and reading ability. Reading ability in a group of primary school children was compared to performance on a visual cued coherent motion detection task. The results showed that a brief spatial cue was more effective in drawing attention either away or towards a visual target in the group of readers ranked in the upper 25% of the sample compared to lower ranked readers. Regression analysis showed a significant relationship between attentional processing and reading when the effects of age and intellectual ability were removed. Results suggested a stronger relationship between visual attentional and non-word reading compared to irregular word reading.

Analysis of Variance↗

Performance of a bedside C-reactive protein test in the diagnosis of community-acquired pneumonia in adults with acute cough.

PURPOSE: To evaluate the performance of a rapid, bedside whole blood C-reactive protein test as a diagnostic test for pneumonia in adults. METHODS: We enrolled consecutive adults who presented with acute cough (duration < or =3 weeks). A fingerstick blood specimen for C-reactive protein level was obtained. Patients also provided information about demographic characteristics and symptoms. Physical examination findings, diagnoses, and treatments were abstracted from the medical record; illness duration and subsequent office visits were determined with follow-up telephone calls. A clinical prediction rule for pneumonia was calculated for each patient and compared with C-reactive protein levels. RESULTS: Twenty (12%) of the 168 patients in the study had radiographic evidence of pneumonia. Median C-reactive protein levels were significantly higher for patients with pneumonia than in the remaining patients (60 mg/L vs. 9 mg/L, P <0.0001). The area under the receiver operating characteristic (ROC) curve for C-reactive protein level as a predictor of pneumonia was 0.83. C-reactive protein level and the clinical prediction rule were independently associated with pneumonia, yielding a combined area under the ROC curve of 0.93. C-reactive protein level was not associated with hospitalization or resolution of symptoms. CONCLUSION: C-reactive protein levels could be a valuable addition to clinical prediction rules for pneumonia. A C-reactive protein level > or =100 mg/L might be a useful indication for chest radiography or empiric antibiotic therapy when the diagnosis of pneumonia is in doubt.

Adult↗

A rare craniofacial cleft: numbers 7, 2, and 3 clefts accompanied by a single median lip pit.

OBJECTIVE: A unique case of a unilateral partial Tessier no. 7 cleft accompanied by no. 2 and 3 clefts along with a single median lip pit is presented. The history, genetics, epidemiology, classifications, embryology, pathogenesis, and correction techniques are briefly reviewed. After an extensive review of the literature, we conclude that this particular constellation of anomalies has not previously been described.

Cleft Lip↗

Ancient maize from Chacoan great houses: where was it grown?

In this article, we compare chemical (87Sr/86Sr and elemental) analyses of archaeological maize from dated contexts within Pueblo Bonito, Chaco Canyon, New Mexico, to potential agricultural sites on the periphery of the San Juan Basin. The oldest maize analyzed from Pueblo Bonito probably was grown in an area located 80 km to the west at the base of the Chuska Mountains. The youngest maize came from the San Juan or Animas river floodplains 90 km to the north. This article demonstrates that maize, a dietary staple of southwestern Native Americans, was transported over considerable distances in pre-Columbian times, a finding fundamental to understanding the organization of pre-Columbian southwestern societies. In addition, this article provides support for the hypothesis that major construction events in Chaco Canyon were made possible because maize was brought in to support extra-local labor forces.

Archaeology↗

Maternal neuronal antibodies associated with autism and a language disorder.

Neurodevelopmental disorders could be caused by maternal antibodies or other serum factors. We detected serum antibodies binding to rodent Purkinje cells and other neurons in a mother of three children: the first normal, the second with autism, and the third with a severe specific language disorder. We injected the serum (0.5-1.0 ml/day) into pregnant mice during gestation and found altered exploration and motor coordination and changes in cerebellar magnetic resonance spectroscopy in the mouse offspring, comparing with offspring of mice injected with sera from mothers of healthy children. This evidence supports a role for maternal antibodies in some forms of neurodevelopmental disorder.

Adult↗

Globus pallidus internus deep brain stimulation for dystonic conditions: a prospective audit.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured target in the treatment of patients with dystonia. The results of 25 consecutive patients with medically intractable dystonia (12 with generalised dystonia, 7 with spasmodic torticollis, and 6 with other types of dystonia) treated with GPi stimulation are reported. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS benefited all groups, resulting in clear and progressive improvements in their condition. This study clearly demonstrates that DBS of the GPi provides amelioration of intractable dystonia.

Adolescent↗

Visual motion sensitivity and reading.

Reading is more difficult than speaking because an arbitrary set of visual symbols must be rapidly identified, ordered and translated into the sounds they represent. Many poor readers have particular problems with the rapid visual processing required for these tasks because they have a mild impairment of the visual magnocellular system. This deficit has been demonstrated using neuropathological, evoked potential, functional magnetic resonance imaging and psychophysical techniques. The sensitivity of the M-system in both good and bad readers correlates with their orthographic abilities, suggesting that the M-system plays an important part in their development. This role is probably to mediate steady direction of visual attention and eye fixations on words. Thus many children with reading difficulties have unsteady eye control and this causes the letters they are trying to read to appear to move around, so that they cannot tell what order they are meant to be in. Therefore, boosting M-performance using yellow filters, or training eye fixation, can improve reading performance very significantly. Several genetic linkage studies have associated reading difficulties with the MHC control region on the short arm of chromosome 6. This system has recently been shown to help regulate the differentiation of M-cells. This association could also explain the high incidence of autoimmune conditions in poor readers. Other chromosomal sites are associated with the metabolism of polyunsaturated fatty acids (PUFAs) as found in fish oils, and this could explain why PUFA supplements can improve reading.

Attention↗