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Charles J. Hodge Jr.

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Charles J. Hodge Jr., Charles I. Woods and Jonathan Delatizky

✓ There is anatomical, pharmacological, and physiological evidence that descending systems from the brain stem using noradrenalin and serotonin (5-hydroxytryptamine, 5-HT) participate in the control of segmental sensory processing. Study of these systems is described in this paper. L-dopa was given intravenously to cats to cause the release of noradrenalin and 5-HT. The resultant effects on the responses of dorsal horn cells to innocuous and noxious thermal stimulation of skin were determined. Using the catecholamine cell neurotoxin, 6-hydroxydopamine, the dopamine α-hydroxylase inhibitor, fusaric acid, and the tryptophan hydroxylase inhibitor, parachlorophenylalanine, the available central stores of noradrenalin or 5-HT were altered, thus allowing separation of the effects of noradrenalin and 5-HT release on dorsal horn cells. The results indicate that noradrenalin facilitates the responses of dorsal horn cells to innocuous cutaneous stimuli, and has an inhibitory effect on the responses to noxious stimuli. Serotonin inhibits the responses of dorsal horn cells that respond to noxious stimuli, to both innocuous and noxious stimuli. The results are discussed in light of current developments concerning aminergic control of segmental sensory processing.

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Charles J. Hodge Jr., A. Vania Apkarian and Richard T. Stevens

✓ The Kölliker-Fuse nucleus (KF) in the dorsolateral pons has been shown to be the major source of catecholamine innervation of the spinal cord. This has important implications in terms of pain control mechanisms, since catecholamine-mediated mechanisms are essential for the expression of opiate and other varieties of antinociception. This study examines the effects of KF stimulation on responses of dorsal-horn cells to innocuous and noxious cutaneous stimuli in anesthetized cats. Stimulation of the KF potently inhibits the responses of dorsal-horn cells to both noxious and innocuous stimuli. The threshold for the inhibitory effect is significantly lower for responses to noxious stimuli as opposed to innocuous stimuli. The inhibitory effect is specific to the stimulus site, as evidenced by a marked decrease in the effect following small changes in the position of the stimulating electrode in the brain stem. The latency of the effects indicates a bulbospinal conduction velocity of 4 to 5 m/sec, which is much slower than usual reticulospinal effects and is consistent with a catecholamine-mediated system. The dependence of KF-spinal inhibition on intact biogenic amines was tested by depleting the animals of these amines with reserpine pretreatment. Depletion of biogenic amines resulted in a significant decrease in the KF spinal inhibitory effects, suggesting their dependence on intact noradrenergic stores. The results of these studies are consistent with the idea that the KF-spinal system plays an important noradrenergic-dependent role in the brain-stem modulation of spinal processing of noxious, potentially painful stimuli.

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Charles J. Hodge Jr. and Robert B. King

✓ The authors describe a patient with subarachnoid hemorrhage from an arteriovenous malformation of the choroid plexus and present a brief review of related reports.

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Charles J. Hodge Jr. and Robert B. King

✓ The authors describe the sensory examinations of three patients who had undergone cervical rhizotomy alone and in combination with trigeminal tractotomy and section of the nervus intermedius, the glossopharyngeal nerve, and the upper portion of the vagus nerve. Following administration of L-dopa there was an increase in their pain and a decrease in the area of clinically anesthetic or analgesic skin. When methyldopa was given, the subjective and objective changes were the opposite of those elicited by L-dopa. These observations support the existence of a wider dorsal root cutaneous distribution than is usually accepted as well as significant control of cutaneous sensation by suprasegmental areas of the central nervous system. Part of the suprasegmental bias supplied to the area in the spinal cord that processes sensory information apparently occurs by way of an aminergic descending reticulospinal tract. These findings are discussed in terms of attempts totally to denervate restricted cutaneous areas of the body for treatment of pain-producing states.

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Bruce Frankel, Sharon L. Longo, Gerard S. Rodziewicz and Charles J. Hodge Jr.

Object. Available therapies for Cushing's disease are often inadequate or involve the risk of significant morbidity. Accordingly, the need arises for the development of novel treatments, especially for cases caused by corticotroph hyperplasia, a condition difficult to treat using standard therapies. In this study, the authors investigated the use of phosphorothioate antisense oligonucleotides as a potential treatment for Cushing's disease.

Methods. Corticotrophs, obtained from a patient with Cushing's disease in whom pathological findings showed multifocal areas of corticotroph adenoma and hyperplasia, were grown in tissue culture. By assessing cell viability and using immunoradiometric assay techniques, it was determined that these cells grew autonomously and secreted adrenocorticotropic hormone (ACTH) in vitro. A fully phosphorothioated antisense oligonucleotide was constructed to be complementary to the first 25 bp of the region coding for ACTH in exon 3 of the proopiomelanocortin precursor. After incubation of the corticotrophs with liposome-coated phosphorothioate antisense oligonucleotides, a greater than 90% decrease in ACTH release was noted on Days 3 and 6, compared with nonsense-treated controls (p < 0.05).

Conclusions. Antisense oligonucleotides may prove to be a useful adjunct in treating Cushing's disease by targeting one of its fundamental problems, ACTH hypersecretion.

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Cordell E. Gross, Charles J. Hodge Jr., Eugene F. Binet and Irvin I. Kricheff

✓ The authors describe a case in which a subarachnoid block caused by a thoracic vertebral hemangioma was relieved during percutaneous embolization of the tumor.

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Charles J. Hodge Jr., Sean C. Huckins, Nikolaus M. Szeverenyi, Michael M. Fonte, Jacob G. Dubroff and Krishna Davuluri

Object. Functional magnetic resonance (fMR) imaging was performed in human volunteers to determine the lateral perisylvian cortical areas activated by innocuous cutaneous stimulation.

Methods. Eight volunteers who underwent 53 separate experiments form the basis of this report. Eight contiguous coronal slices were obtained using echoplanar fMR imaging techniques while participants were at rest and while somatosensory activation stimuli consisting of vibration or air puffs were delivered to various body areas. The data were analyzed using Student's t-test and cluster analysis to determine significant differences between the resting and activated states. The findings were as follows: the areas in the lateral cortex activated by the sitmuli were the primary sensory cortex (SI), the second somatosensory area (SII), the insula, the superior parietal lobule, and the retroinsular parietal operculum (RIPO). Somatotopy was demonstrable in SI but not in the other areas identified. There was a surprisingly low correlation between the amount of cortex activated in the various areas, which could mean separate inputs and functions for the areas identified. The highest correlation was found between activity in SII and RIPO (0.69).

Conclusions. The authors maintain that fMR imaging can be used to identify multiple lateral somatosensory areas in humans. Somatotopy is demonstrated in SI but not in the other lateral cortical sensory areas. The correlations between the amounts of cortex activated in the different lateral sensory areas are low. Recognition of the multiple lateral sensory areas is important both for understanding sensory cortical function and for safe interpretation of studies designed to identify the central sulcus by activating SI.

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Aneela Darbar, Richard T. Stevens, Adnan H. Siddiqui, James S. McCasland and Charles J. Hodge

Object

The brain shows remarkable capacity for plasticity in response to injury. To maximize the benefits of current neurological treatment and to minimize the impact of injury, the authors examined the ability of commonly administered drugs, dextroamphetamine (D-amphetamine) and phenytoin, to positively or negatively affect the functional recovery of the cerebral cortex following excitotoxic injury.

Methods

Previous work from the same laboratory has demonstrated reorganization of whisker functional responses (WFRs) in the rat barrel cortex after excitotoxic lesions were created with kainic acid (KA). In the present study, WFRs were mapped using intrinsic optical signal imaging before and 9 days after creation of the KA lesions. During the post-lesion survival period, animals were either treated with intraperitoneal D-amphetamine, phenytoin, or saline or received no treatment. Following the survival period, WFRs were again measured and compared with prelesion data.

Results

The findings suggest that KA lesions cause increases in WFR areas when compared with controls. Treatment with D-amphetamine further increased the WFR area (p < 0.05) while phenytoin-treated rats showed decreases in WFR areas. There was also a statistically significant difference (p < 0.05) between the D-amphetamine and phenytoin groups.

Conclusions

These results show that 2 commonly used drugs, D-amphetamine and phenytoin, have opposite effects in the functional recovery/plasticity of injured cerebral cortex. The authors' findings emphasize the complex nature of the cortical response to injury and have implications for understanding the biology of the effects of different medications on eventual functional brain recovery.

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Tracy E. Alpert, Seung S. Hahn, Chung T. Chung, Jeffrey A Bogart, Charles J. Hodge and Craig Montgomery

✓ A primary spindle cell sarcoma of the sella turcica in a patient without a history of radiation treatment is a very rare occurrence. Only one other case has been reported to date, with local recurrence 7 months after the patient underwent subtotal resection and stereotactic radiosurgery of the tumor.

The authors present a case of spindle cell sarcoma of the sella turcica successfully treated by surgery, external-beam radiotherapy, and gamma knife radiosurgery. After 24 months of follow up, the patient continues to show no evidence of disease.