Biomedical subjects
Publications and source records attributed to John Stein.
In a patient of generalised dystonia treated with bilateral pallidal stimulation, serial surface EMGs recorded from the neck muscles during alternating head movements revealed progressive reduction in hypertonic activity and reversal of co-contraction to reciprocal contraction, which preceded clinical improvement.
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.
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.
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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.
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.
Chronic deep brain stimulation (DBS) of the periventricular gray (PVG) has been used for the treatment of chronic central pain for decades. In recent years motor cortex stimulation (MCS) has largely supplanted DBS in the surgical management of intractable neuropathic pain of central origin. However, MCS provides satisfactory pain relief in about 50-75% of cases, a range comparable to that reported for DBS (none of the reports are in placebo-controlled studies and hence the further need for caution in evaluating and comparing these results). Our experience also suggests that there is still a role for DBS in the control of central pain. Here we present a series of eight consecutive cases of intractable chronic pain of central origin treated with PVG DBS with an average follow-up of 9 months. In each case, two electrodes were implanted in the PVG and the ventroposterolateral thalamic nucleus, respectively, under guidance of corneal topography/magnetic resonance imaging image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5-35 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency thalamic FPs at 0.2-0.4 Hz closely associated with the pain. During 5-35 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz), however, there was no reduction in the FPs and no pain suppression. We have found an interesting and consistent correlation between thalamic electrical activity and chronic pain. This low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation. It may be possible to use the presence of these slow FPs and the effect of trial PVG DBS on both the clinical status and the FPs to predict the probable success of future pain control in individual patients.
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OBJECTIVE: Continuous nebulization is becoming more popular in the management of acute bronchospasm in the emergency department (ED). Controversy still exists as to the optimal dose of albuterol for such exacerbations. The present study hypothesis was that there is no difference between continuous nebulization of albuterol at 7.5 mg/hr (usual dose) and 15 mg/hr (high dose) in peak flow improvement up to three hours. METHODS: This was a randomized, controlled, double-blind trial, set in an urban county teaching ED. One hundred twenty-seven patients with acute bronchospasm and an initial peak flow (PF) less than 75% predicted were enrolled. Patients were randomized to usual-dose (UD) or high-dose (HD) groups along with a standard treatment protocol. Primary end-points were analyzed using repeated-measures analysis of variance (ANOVA), and 95% confidence intervals (95% CIs) are given for such variables. RESULTS: Sixty-seven patients were randomized to the HD albuterol group, and 63 completed the study. Sixty patients were randomized to the UD group, and 55 completed the study. Repeated-measures ANOVA found no difference in systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, Borg dyspnea scale score, and peak flow over time between the groups. The mean (+/-SD) peak flow improvement at one hour was UD 51 (+/-49) L/min vs. HD 45 (+/-50) L/min, mean difference 6.8 L/min (95% CI = -11 to 24.9 L/min). Adjusting for baseline, the percentage increase in peak flow at one hour was UD 44% (+/-60%) vs. HD 30% (+/-40%), mean difference 14% (95% CI = -4.4% to 32.4%). Time to disposition showed a mean of 188 (+/-129) minutes for UD and 230 (+/-183) minutes for HD, mean difference 42 minutes (95% CI = -170 to 101 min). One patient in the HD group was intubated. Admission rate was UD 70.9% vs. HD 65%, mean difference 5.9% (95% CI = -10.9% to 22.7%). CONCLUSIONS: In treating acute, moderately-severe bronchospastic ED patients with peak flow less than 75% of predicted with albuterol by continuous nebulization, 15 mg/hr appears to offer no advantage over 7.5 mg/hr in peak flow improvement or length of stay in the ED.
The causes of dyslexia are unknown, but previous studies have suggested an immunological basis in some cases. We hypothesised that maternal antibodies, which cross the placenta and bind to fetal antigens, could be responsible, particularly when the dyslexia recurs in consecutive pregnancies. We injected serum samples from five mothers of two or more children with dyslexia into pregnant mice, and tested the offspring for behavioural abnormalities and cerebellar metabolites by magnetic resonance spectroscopy (MRS). Mice exposed in utero to serum factors from one woman with two dyslexic children, who had also had three spontaneous fetal losses, showed deficits in motor tests which correlated with cerebellar choline (Cho) and creatine (Cr) levels. These preliminary results are consistent with a role for maternal serum factors, probably antibodies, in causing some of the features of dyslexia, and possibly in other neurodevelopmental disorders.
Stimulation of the central gray matter areas has been used for the treatment of chronic pain for decades. To better understand the mechanism of action of such treatment we studied the effects of stimulation of the periventricular gray (PVG) on the sensory thalamus in two patients with chronic central pain. In each case, two electrodes were implanted in the PVG (Medtronic 3389) and the ventroposterolateral thalamic nucleus (Medtronic 3387), respectively, under guidance of CT/MRI image fusion. The PVG was stimulated in the frequency range of 2-100 Hz in alert patients while pain was assessed using the McGill-Melzack visual analogue scale. In addition, local field potentials (FPs) were recorded from the sensory thalamus during PVG stimulation. Maximum pain relief was obtained with 5-25 Hz stimulation while 50-100 Hz made the pain worse. This suggests that pain suppression was frequency dependent. Interestingly, we detected low frequency FPs at 0.2-0.4 Hz closely associated with the pain. During 5-25 Hz PVG stimulation the amplitude of this potential was significantly reduced and this was associated with marked pain relief. At the higher frequencies (50-100 Hz) however, there was no reduction in the FPs and no pain suppression. We have found an interesting correlation between thalamic activity and chronic pain. This curious low frequency potential may provide an objective index for quantifying chronic pain, and may hold further clues to the mechanism of action of PVG stimulation.
Central post stroke pain is often difficult to manage satisfactorily with conventional treatment modalities for pain. In the last decade functional neurosurgery has offered hope with motor cortex stimulation achieving significant alleviation of pain in some patients. Unfortunately this has led to the neglect of chronic stimulation of deep grey matter as another modality of treating this condition. In this article we present our experience with motor cortex stimulation and that with deep grey matter stimulation in patients with post stroke pain. We argue that both modalities have a significant role and that what is required are better methods of identifying particular patients who are more likely to respond to one or the other.
It has been demonstrated that selective unilateral surgical ablation of posteroventral globus pallidus interna relieves the movement disorders associated with advanced Parkinson's disease, without necessarily incurring the executive cognitive sequelae that have been observed following gross pathological lesions to this brain region. This finding is consistent with established theory that underlying neuronal circuitry is functionally segregated into parallel cortico-striatal-pallidal-thalamo-cortical 'loops'. We have studied a series of 12 patients with advanced Parkinson's disease at baseline, and then following bilateral pallidotomy, with a battery of neuropsychological tests including the Cambridge Neuro psychological Test Automated Battery. We identified a selective and universal loss of individual patients' ability to shift attention to novel dimensions in a test of abstract rule-learning following surgery, which was not reliably associated with any other change in cognition, personality, mood or medication. This finding is rare in its specificity and has implications for theoretical models of the functional architecture and pathophysiology of the globus pallidus, and the clinical practice of pallidotomy.
The authors report the neurological, neurophysiological, and neuropsychological effects of using long-term bilateral pallidal high-frequency deep brain stimulation (DBS) in a case of disabling camptocormia. Deep brain stimulation electrodes were implanted stereotactically to target the globus pallidus internus (GPi) bilaterally. Local field potentials (FPs) were recorded using the DBS electrodes and concurrent abdominal flexor electromyography (EMG) potentials during camptocormic episodes. Videotaped assessments of the movement disorder and neuropsychological evaluations of the patient before implantation and 6 months after initiation of pallidal stimulation were recorded. There was significant functional improvement following long-term pallidal stimulation, and some improvement was noted in neuropsychological scores. A temporal correlation between the GPi FPs and EMG-recorded rectus abdominis potentials was evident. There were no treatment-related adverse effects. The authors have found that long-term pallidal stimulation was safe and offered functional benefit to a patient with this severely disabling condition. The physiological studies may help further the understanding of the pathophysiology of this rare entity.