bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Continuous Vibration on Sural Nerve Action Potentials
Authors: Ertekin Nezihe , Çitakoğlu Kerime , Ertekin Cumhur
Published: May 2007

The effects of continuous vibration on sural nerve action potentials were investigated in 15 subjects. The results show that continuous vibration applied to the sural nerve innervated skin area produces an amplitude reduction of the sural nerve action potentials on both painless and painful stimulation conditions. This amplitude decrease is attributed to an impulse blockage of the large diameter afferent nerve fibers.
Involvement of Glycogen Synthase Kinase-3β in Palmitate-Induced Human Umbilical Vein Endothelial Cell Apoptosis
Authors: Choi Sung-E. , Kang Yup , Jang Hyun-Ju , Shin Ha-Chul , Kim Hyo-Eun , Kim Hyo-Soo , Kim Hae Jin , Kim Dae Jung , Lee Kwan-Woo
Published: May 2007

Background/Aims: The death of endothelial cells may play a critical role in the development of various vascular diseases, including atherosclerosis. While free fatty acids (FFAs) may stimulate endothelial apoptosis, the molecular and cellular mechanisms of this effect have not been studied intensively. To elucidate the mechanisms involved in FFA-induced endothelial cell apoptosis, we investigated the effect of different pharmacological inhibitors on palmitate-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Interestingly, lithium, a glycogen synthase kinase-3 (GSK-3) inhibitor, showed a strong protective effect. Methods and Results: To examine the involvement of GSK-3β in palmitate-induced HUVEC apoptosis, its dephosphorylation at Ser9 and enzymatic activation in response to palmitate treatment were monitored by immunoblotting and in vitro kinase assays, respectively. GSK-3β was dephosphorylated and its enzymatic activity increased in palmitate-treated HUVECs. In addition, pretreatment with other GSK-3β inhibitors, e.g. SB216763 or TDZD-8, as well as adenoviral transduction with a catalytically inactive GSK-3β had significant protective effects against palmitate-induced HUVEC apoptosis. Conclusion: These results demonstrate that the GSK-3β signalling pathway is involved in palmitate-induced HUVEC apoptosis.
Skin Potential and EMG Changes Induced by Cutaneous Electrical Stimulation
Authors: Procacci Paolo , Francini Fabio , Maresca Marco , Zoppi Massimo
Published: May 2007

In a group of patients suffering from reflex sympathetic dystrophies, the skin potential and EMG responses induced by electrical stimuli applied to the skin were recorded in the four limbs in order to study somato-sympathetic and so-mato-motor reflexes. In most patients, the amplitude, delay and shape of the cutaneous responses as well as the pattern of the EMG responses were different from those observed in normal subjects. In particular, it was possible to correlate the pattern of the cutaneous and muscular responses with the severity of the disease. The cutaneous sensory thresholds to electrical stimuli (tactile, tingling and pain threshold) showed different values in the dystrophic and in the contralateral limb. In all patients, a block of the sympathetic chain ipsilateral to the dystrophic limb was performed with local anesthetics. 1 h after the block, the cutaneous responses disappeared not only in the blocked limb but also in the contralateral limb. 48 h after the block, muscular and cutaneous responses as well as sensory thresholds showed a pattern similar to that observed in normal subjects. These findings show that the sympathetic block provides a resetting of the sensory thresholds and reflexes.
Effect of Propranolol on Monosynaptic Reflex Activity during a Task
Authors: Brunia C.H.M.
Published: May 2007

20 normal healthy subjects in a double-blind crossover experiment were given a tablet of either 40 mg propranolol or placebo half an hour before the beginning of the experiment. At rest and during the performance of a task, heart rate, Achilles tendon (T) and Hoffmann (H) reflexes were recorded. No increase in heart rate occurred during the task in the propranolol session. The increase of T-reflex amplitude, a common finding during the task under consideration, was larger in the propranolol session. No difference with H reflexes was found. It is concluded that the increase of T-reflex amplitudes during the task is caused only by fusimotor and not by sympathetic activity. It is speculated that if the sympathetic system plays a role at all, the effect on the T reflex is depressive rather than facilitating.
Influence of Temporal Lobe Lesions on Photic-Evoked Responses in Occipital Visual Areas
Authors: Arseni C. , Crighel E. , Matei M. , Dinu M.
Published: May 2007

In 20 patients with temporal lobe lesions and 10 controls, the averaged photic-evoked responses (APERs) and their dispersion pattern (DP) were investigated in inion-vertex-lead and bilaterally in inion-parietal leads (I-P3 and I-P4). The patients with temporal lobe lesions, regardless of lesion location in temporal areas, displayed either absence of APER (the whole APER or only the initial components) or a latency increase without amplitude changes. The DP was generally abnormal. The role of the temporal lobe in the organization of APER in visual areas is discussed.
TNS-Evoked Long Loop Effects
Authors: Hiedl P. , Struppler A. , Gessler M.
Published: May 2007

Local analgesia can be produced by transcutaneous electrical stimulation of peripheral nerves. This is used in the treatment of chronic pain states. lts clinical effectiveness depends on two points; namely (1) the stimulation has to be perceptible, and (2) paresthesias elicited by TNS must be localized in the area of pain. To verify this in healthy subjects we produced an experimental pain by radiant heating of the skin and tested the analgesic effect of TNS. TNS stimuli parameters (duration, amplitude and frequency) were determined so that double blind conditions were given. Stimulation with small rectangular pulses showed the best analgesic effect especially at a stimulation rate of 100 Hz. The stimulation of various nerves showed that most of the analgesic effects depend on spinal level mechanisms but probably long loop effects are involved.
Thalamic Recordings during Stereotactic Surgery
Authors: Hardy Tyrone L. , Bertrand Gilles , Thompson C.J.
Published: May 2007

With the aid of a computer graphic technique, data gathered from exploratory recordings of the diencephalon in 130 stereotactic operative procedures is presented to show the topographical distribution of evoked and nonevoked thalamic rhythmic cellular activity.
Effect of Papaverine on Regional Cerebral Blood Flow of the Contralateral Hemisphere in Patients with Acute Cerebral Infarction
Authors: Melamed E. , Lavy S.
Published: May 2007

The effect of intravenously administered papaverine hydrochloride on the regional cerebral blood flow (rCBF) was determined in the contralateral hemispheres of 6 patients with acute unilateral cerebral infarction. In all 6 patients, the resting state rCBF was reduced in the noninfarcted hemisphere. Papaverine increased the hemispheric mean rCBF in only 1 patient, whereas abnormal responses were observed in 5 subjects. Mean hemispheric flow values decreased paradoxically in 2 patients and remained unchanged in 3. Individual rCBF values increased in the entire contralateral hemisphere in 1 patient. Widespread paradoxical rCBF decreases were observed in another subject. Mixed regional responses to papaverine, showing decreases, no change and increases in rCBF values occurred in the opposite hemispheres of 4 patients. These findings provide additional evidence that the chem-ical control of rCBF may be impaired in the contralateral ‘unaffected’ hemisphere soon after the onset of acute cerebral infarction.
Effects of Maternal Administration of Endoxan, Vitamin A and Vitamin B12 on the Development of the Fetal Spinal Cord of the Albino Mouse
Authors: Nawar Nabil N.Y. , Sakla François B. , Mahran Zaghloul Y.
Published: May 2007

The effects of maternal administration of endoxan, vitamin A and vitamine B12 were studied on the cervical fetal spinal cord of the albino mouse. Endoxan caused dorsal and ventral herniation of the spinal cord, chromatolysis and degeneration of the neuroblasts together with neuroglial proliferation. Vitamin A and B12 resulted in an increase in the surface areas of both grey and white matter and an increase in the volume of the neuroblasts. The possible mechanisms concerned were discussed.
Electronystagmography in Neurological Diagnosis
Authors: Toglia Joseph U.
Published: May 2007

Electronystagmography (ENG) is a technique for recording nystagmus and other eye movements; our technique, based on the utilization of a bioelectrical potential which exists between the retina and the cornea, has been reported in detail elsewhere in a monograph [29]. ENG has been used particularly by otologists to record caloric nystagmus and study labyrinthine function [2, 4, 16, 19]. This technique should have even greater applications in the diagnosis of neurological disease, since nystagmus and abnormalities of ocular and vestibular functions are symptoms frequently encountered by the neurologist. This paper illustrates this point with three case reports.
Hemiballismus Complicating Stereotactic Thalamotomy
Authors: Modesti Luciano M. , Van Buren John M.
Published: May 2007

The pathology of poststereotactic hyperkinesis has been rarely documented and the pathophysiology is still poorly understood. In a case of hemiballismus following thalamotomy for parkinsonism, detailed anatomical studies showed bilateral cortical pseudolaminar necrosis and no involvement of the subthalamic nuclei by the thalamic lesions. The structural and functional effects of surgical lesions upon the preexisting pharmacological abnormalities present in parkinsonism probably constitute the substrate necessary for occurrence of hemiballismus following stereotactic surgery.
Mesencephalic Chronic Electrodes in Pain Patients
Authors: Strassburg H.M. , Thoden U. , Mundinger F.
Published: May 2007

Early components of lemniscal potentials after contralateral median nerve or mechanical stimulus are due to lemniscal pathways, whereas later components, after 70 msec appearing bilaterally and at higher stimulus intensities probably express extralemniscal activity. Evoked potentials in the central gray matter show much smaller amplitudes compared with somatosensory cortical evoked potentials (SSEP). The strongest component is a negative wave after 70–100 msec. Longer conditioning stimulation of the lemniscal system inhibits late components in the median nerve evoked cortical potentials. On the contrary, stimulation of the nonspecific periaqueductal gray matter produces inhibition of early components of cortical SSEP together with facilitation of late components.
Cross-Correlation Analysis of the Lateral Pulvinar and Scalp EEG in Man
Authors: Fujita Shigekiyo , Fujita Katsuzo , Matsumoto Satoshi
Published: May 2007

Cross-correlation analysis of the EEG between the lateral pulvinar and various cortical regions was made after EEG was recorded during stereotactic pulvinectomy. Cross-correlation analysis of the α-waves between the lateral pulvinar and the scalp EEG showed that the lateral pulvinar has the highest degree of functional connection with the pre-central area, diminishing in degree with the parietal and frontal areas, and has poor functional connections with the occipital area. From these results, it might be concluded that the lateral pulvinar may be related to motor function by functional connections with the pre-central area rather than the parietal area.
Diagnosis of Electric Neurostimulating Device Dysfunction
Authors: Meyer Paul G. , Nashold Jr. Blaine S. , Peterson Jack
Published: May 2007

The recent advances in the area of electric neurostimulating devices have added important tools to the neurosurgeon in the treatment of numerous clinical problems. The diagnosis of equipment dysfunction poses a unique problem for the physician. This communication presents methods of testing these electric neurostimulating systems using the basic equipment found in any electronics laboratory.
Dissolution of Smooth Platinum Electrodes in Biological Fluids
Authors: Black R.C. , Hannaker P.
Published: May 2007

Quantitative measurements of the dissolution of smooth platinum electrodes resulting from stimulation of physiological saline with sinusoidal, square biphasic, square monophasic and direct currents have been made by spectrophotometric analysis of the stimulated solution. Results presented give an indication of the stimulus parameter region in which platinum dissolution is minimal and therefore potentially suitable as an implant electrode material.
Transabdominal Neurostimulation in Treatment of Neurogenic Ileus
Authors: Richardson Robert R. , Cerullo Leonard J.
Published: May 2007

Transabdominal neurostimulation (TANS) is an innovative concept used in the treatment of neurogenic ileus, which frequently follows chronic spinal cord or neurological lesions. It was used in the treatment of neurogenic ileus in 21 patients at Northwestern Memorial Hospital with rapid resolution of the ileus, elimination of nasogastric tubes, and institution of oral feedings soon after application. Major advantages in using TANS are effective resolution of ileus, ease of application, and lack of major gastrointestinal complications, especially those produced by nasogastric tubes.
Stereotactic Amygdalotomy for Convulsive and Behavioral Disorders
Authors: Heimburger R.F. , Small Iver F. , Small Joyce G. , Milstein Victor , Moore Donald
Published: May 2007

58 patients, whose convulsions and behavioral disorders did not respond to nonsurgical therapy, were treated with stereotactic amygdalotomy between 1963 and 1973. A retrospective study was carried out by a psychiatric research team 1–11 years postoperatively. Using reliable objective methods of assessment they found that 50% operated primarily for seizures, 33% for uncontrolled conduct disorders and 50% with both conditions seemed improved after surgery.
Percutaneous Central Gray Stimulation for Cancer Pain
Authors: Meyerson B.A. , Boëthius J. , Carlsson A.M.
Published: May 2007

Electrical stimulation of the periventricular and periaqueductal gray matter via a percutaneous electrode appears to be a useful method for relieving cancer pain with midline and bilateral distribution. Due to the nondestructive character and the minor surgical risks involved in this procedure it may be tried before considering bilateral cordotomy or myelotomy. A possible mechanism of action or at least a contributive factor to the pain relief is the activation of endorphins.
Changes in Regional Cerebral Blood Flow Following Stereotactic Psychosurgery
Authors: Kullberg Gunvor , Risberg Jarl
Published: May 2007

Serial measurements of regional cerebral blood flow by the 133Xe inhalation method were performed in a pilot study in 6 patients undergoing stereotactic psychosurgical procedures (anterior capsulotomy, cingulotomy, frontobasal tractotomy). Average hemispheric flow did not change significantly from pre- to post-operative, but changes were seen in the patterns of regional flow distribution. The most striking finding was frontal flow reduction following capsulotomy. In view of the coupling of blood flow and function in the brain, the results indicate that this method offers a new way for exploring the effects of functional neurosurgery on brain activity.
Treatment of Spasmodic TorticoIIis by DorsaI Column Stimulation
Authors: Gildenberg Philip L.
Published: May 2007

A new method is described to treat spasmodic torticollis with the implantation of a dorsal column stimulator at the C1–2 level or with transcutaneous stimulation. 22 patients were evaluated. 3 had sufficient relief to be treated with transcutaneous stimulation only. An additional 6 patients had surgically implanted dorsal column stimulators. It was empirically determined that a frequency of 800–1,100 Hz gave the best relief from torticollis. 1 patient had an excellent result; 3 have had good results; 1 had a fair result, and 1 had a poor result. An additional patient with dystonia musculorum deformans was considerably improved by the use of dorsal column stimulation.
Contribution of Trigeminal and Facial Reflexes to the Localization of Vth, VIIth, and VIIIthCranial Nerve Dysfunction
Authors: Molina Pierre , Hardy Jules , Bertrand Robert A.
Published: May 2007

After a review of electrophysiological studies in 1,500 cases concerning different types of lesions of the trigeminal nerve, the acousticofacial complex, and the brain stem, one can conclude that beside the intensive clinical examination which most often allows a precise topographic diagnosis, study of trigeminofacial and facial reflexes appears to be an essential diagnostic method to determine the topography of the lesions. On the other hand, this study can sometimes contribute to the prognostic evaluation as well as the choice of the approach in some lesions concerning the acousticofacial complex.
Estimation of Neural Noise
Authors: Nakajima Hideo , Fukamachi Akira , Isobe Itsuo , Miyazaki Mizuho , Shibazaki Thoru , Ohye Chihiro
Published: May 2007

In the course of stereotactic thalamotomy, the neural noise level of subcortical structures was estimated quantitatively with the aid of two semimicro-electrodes. The neural noise showed several characteristic features in terms of its amplitude and discharge pattern so that it was correlated with the possible anatomical substrate, thus providing the functional anatomy of the subcortical structures. The study on sagittal plane revealed a systematic difference of the noise level between VL and Vim-Vc that could be explained by the different cell size in respective nucleus. Several exceptional cases were also presented, emphasizing the neural noise study in stereotactic surgery.
Motivational Slow Negative Potential Shift (CNV) Related to Thalamotomy
Authors: Tsubokawa Takashi , Moriyasu Nobuo
Published: May 2007

The alteration of cortical electrical activity induced by imperative stimulation following warning stimulation, contigent negative variation (CNV), and psychological changes following thalamotomy for relief of intractable pain (CM) and tremor (VL) are studied, since CNV has a close relationship with the degree of psychological activity. Ventrolateral thalamotomy does not have any effect on the amplitude of cortical CNV, but the ventromedioposterior part of the centre median has a generating action of CNV in itself and it has facilitatory effects upon cortical CNV. According to these results, the effective mechanism of centre median thalamotomy for relief of intractable pain is caused by suppression of attention and expectancy for exogenous stimuli following lesions of the centre median.
Stereotactic Radiofrequency Hypophysectomy
Authors: Zervas N.T. , Hamlin H.
Published: May 2007

Clinical indications and technical details of RF hypophysectomy were reviewed. Evaluation of several hundred procedures toward pathologic and symptomatic amelioration of metastatic breast cancer and diabetic retinopathy, and also a few cases of intrasellar tumor, indicated sufficient benefit for endorsement in selected patients.
The Posteromedial Hypothalamus and Pain, Behavior, with Special Reference to Endocrinological Findings
Authors: Mayanagi Y. , Hori T. , Sano K.
Published: May 2007

Stereotactic intervention into the posterior hypothalamus gives satisfactory results for controlling both aggressive, violent behavioral disorders and intractable pain. From the endocrinological point of view, this procedure activates the hypothalamic-hypophyseal axis only temporarily, without causing any serious dysfunctions.
Stereotactic Brain Surgery: a Method for Rapid and Precise Positioning of a Target in the Todd-Wells Stereotactic Instrument
Authors: Nadelhaft I. , Morgan C. , Herbert D.L.
Published: May 2007

We describe an improved method for positioning the head for stereotactic brain surgery of aneurysms. The method uses a mathematical calculation and requires some physical modifications in the Todd-Wells stereotactic apparatus. This procedure achieves (1) a reduction in the number of angiograms needed and (2) an increase in the speed and accuracy of positioning. The technique has been applied to operations on live dogs.
Functional Ablation by Spreading Depression: Possible Use in Human Stereotactic Neurosurgery
Authors: Šramka M. , Brožek G. , Bureš J. , Nádvorník P.
Published: May 2007

Spreading depression (SD) of EEG activity was elicited by microinjection (5 µl) of 5% potassium chloride into the caudate nucleus (n = 7) or hippocampus (n = 3) during stereotactic brain surgery in patients with focal epilepsy. An electrode-cannula assembly for eliciting and recording the slow potential waves of SD is described. The parameters of SD in human brain are similar to those in lower mammals. Functional ablation by SD can be used as a diagnostic tool in neurosurgery.
Adverse Effects of Electrical Energy Applied to the Nervous System
Authors: Pudenz Robert H. , Agnew William F. , Yuen Ted G.H. , Bullara Leo A. , Jacques Skip , Shelden C. Hunter
Published: May 2007

Neural prostheses activated by radiofrequency transmission are currently being implanted to treat a variety of clinical problems. It is essential that neither the materials used in these prostheses, particularly the electrodes, nor the stimulus parameters that are employed will cause neural damage. The experiences of investigators engaged in both the experimental laboratory and clinical studies of the effects of electrical stimulation are reported herein.
Technique and Technical Problems Associated with Implantation of Neuroaugmentive Devices
Authors: Adams John E.
Published: May 2007

The effectiveness of implantation of depth electrodes for pain control in (a) the primary thalamic relay nuclei, and (b) the periventricular gray matter or periaqueductal gray matter is reviewed. In a series of 39 patients, 14 achieved relief with no further need for medication, 16 were able to reduce their drug intake and 9 experienced no relief. These results are compared to those for a series of 76 patients reported on by an international study group of neurological surgeons. 61 patients in this series were considered to have had a successful result immediately after implantation of the electrode, but at the time of follow-up only 42 were still in this category. The implantation of depth electrodes requires a technique that fulfills the following criteria: (1) the procedure must be performed in a fully awake, cooperative patient; (2) a precise stereotactic technique must be employed, and (3) the effects of stimulation must be evaluated before the implant is made permanent. The most common complication was infection at the implantation site; this can be reduced by the use of Teflon-insulated percutaneous leads. Other complications include erosion of the hardware through the scalp and internal migration of the electrodes.
Safety and Efficacy of Chronic Cerebellar Stimulation
Authors: Cooper I.S. , Amin I. , Upton A. , Riklan M. , Watkins S. , McLellan L.
Published: May 2007

It is our conclusion that CCS is both efficacious and safe as a therapeutic measure for neurologic disease. As indications become more concise and patients can be chosen who are not as incapacitated as those in our first group, this should become even more apparent. In order to be certain that calibration of the stimulating equipment is accurate each apparatus should be calibrated by the group treating the patient. We are now making this a routine aspect of our follow-up recheck examinations.
Physiological and Histological Effects of Cerebellar Stimulation
Authors: Larson Sanford J. , Sances Jr. Anthony , Hemmy David C. , Millar Edward A. , Walsh Patrick R.
Published: May 2007

Cerebellar implants have been placed in 62 patients with postoperative follow-up of 4 months to 3 years. Initially currents were applied through electrodes of alternate polarity on the superior surface of the cerebellar hemispheres and subsequently through negative electrodes on the superior surface to positive electrodes on the posterior surface. The amount of current required for clinical improvement was approximately the same as that required to significantly reduce the amplitude of the somatosensory evoked potential. The clinical and electrophysiological effects were proportional to the intensity of current and to the number of electrodes through which the currents were applied. Currents applied through the cerebellum were more effective than those confined near the cerebellar surface. Histological examination of the cerebellum from the chimpanzees and from 1 patient who died of causes unrelated to stimulation failed to demonstrate any evidence of neuronal damage related to application of current.
Chronic Dorsal Column Stimulation via Percutaneously Inserted Epidural Electrodes
Authors: North Richard B. , Fischell Tim A. , Long Donlin M.
Published: May 2007

31 patients suffering from intractable pain associated with chronic low back syndrome, terminal cancer, and other disorders have been studied after an average 6 months’ treatment by electrical stimulation of the spinal cord applied via electrodes inserted through a Tuohy needle into the epidural space. As judged by three different subjective rating methods, epidural stimulation successfully relieved otherwise intractable chronic pain in from 23 to 26 of the 31 patients. Reported improvements in the ability to perform various everyday activities, and elimination of drug usage by many patients, corroborate this finding. The side effects of stimulation, both as reported subjectively and as measured objectively by sensory testing, were not clinically significant. Spontaneous electrode displacements, leading to loss of analgesia and requiring minor surgery for repositioning, were encountered frequently, as were lead wire failures necessitating replacement. The partially implanted, externally powered stimulation system presently in use also suffers from problems of reliability and convenience to the patient.
Electrical Stimulation of the Conus medullaris in the Paraplegic
Authors: Nashold jr. Blaine S. , Grimes John , Friedman Harry , Semans James , Avery Roger
Published: May 2007

In 1970 we carried out the first electrode implantation of the conus medullans of a 17-year-old male paraplegic to control the emptying of his paralyzed bladder. Our patient has used electromicturition for 6 years to successfully empty his bladder and prevent urinary infection. To date, a total of 11 paraplegic patients have been implanted (6 males, 5 females). The cause of the paraplegia was the result of trauma, and the implants were performed from 16 days to 15 years postinjury. All the patients had experienced numerous urinary infections and required constant catheter drainage, and it was the opinion of our urologic associate that current methods of control of the bladder problem were of no avail. The bladder was considered to be atonic in 7 patients and spastic in 4. The results indicate that after a follow-up of 1–6 years, 8 patients have complete control of voiding by electrical stimulation (4 female, 4 male). 2 of the males required partial sphincterotomy to improve emptying, but none of the females experienced sphincter interference. One male quadriparetic patient died 7 months postimplantation of pneumonia and hepatitis. There have been no infections related to the implantable device; however, 1 female broke the connecting wires to the spinal cord electrode during a paraplegic basketball game. In addition to the induced electrical contraction of the bladder, we have observed increased autonomic activity below the level of the spinal cord transection, improved defecation, reduction of spasticity in the paralyzed legs, penile erection in males, and reduction of decalcification of the long bones. This group of patients represents the longest use of an implantable electronic device to control bladder function.
Electrostimulation of the Nervous System for Patients with Demyelinating and Degenerative Diseases of the Nervous System and Vascular Diseases of the Extremities
Authors: Dooley Donald M. , Sharkey Jerrold
Published: May 2007

The results of electrostimulation of the spinal cord for symptoms other than that of pain are recorded in this publication. 50% of patients with multiple sclerosis, primary lateral sclerosis and hereditary spino-cerebellar disorders were observed to have enduring favourable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled had the greatest amount of increased function and were benefitted the most by the stimulation. Those who had the fewest neurological pathways affected make the most rapid progress. For example, the patient with only an ataxic or spastic gait was observed to improve faster than the patient with an ataxic and a spastic gait. The long-term effect of electrostimulation of the spinal cord on patients with these diseases is unknown at the present time. The purpose of the stimulation is to increase neurological function so that the patient can live a better life style. It is not thought that the electrical current is responsible for a ''cure'' of the basic disease process. Electrostimulation of the posterior spinal roots and spinal cord, while not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace Standard therapeutic measures of treatment of patients with vascular disease but to supplement them.
Pain Suppression by Peripheral Nerve Stimulation
Authors: Picaza J.A. , Hunter S.E. , Cannon B.W.
Published: May 2007

This is a study of the long range effects of pain suppression obtained by electrical stimulation of peripheral nerves. These cases were followed during 12–46 months and evaluated personally and by questionnaires. Selection for surgery was done exclusively on the basis of the results of a preoperative peripheral nerve stimulation test. Of 37 case observations, 18 were considered significantly relieved; that is, more than 50% of the intensity and/or duration of pain was consistently admitted. The results obtained in the acute preoperative trial could be reproduced indefinitely in some cases for as long as 46 months. Correlation of the results with the disease producing the pain revealed as benefitting for painful syndromes associated with peripheral nerve disorders, amputation, soft tissue injuries (nerves?), and some recurrent lumbar disc surgeries. Sciatic, ulnar and occipital nerve implantations were particularly rewarding. The best and worse results were analyzed. The complications appear to be largely preventable and of no serious consequences. Our analysis suggests that most failures take place within 2 years from implantation. Experience seems to be accumulating showing that a number of patients may receive sustained relief beyond this period.
Evaluation of Electrode Configurations in Cerebellar Implants
Authors: Sances, Jr. Anthony , Larson Sanford J. , Myklebust Joel , Swiontek Thomas , Millar Edward A. , Cusick Joseph F. , Hemmy David C. , Jodat Ronald , Ackmann James
Published: May 2007

Capacitively coupled currents of 100 Hz, 0.25 msec duration, were applied to multielectrode arrays implanted upon the superior and posterior surfaces of the chimpanzee cerebellum. The current required for 90% reduction in the amplitude of the evoked potential was inversely proportional to the number of electrodes upon the cerebellar surface. A study of various waveforms showed that a 100 Hz, 0.25 msec pulse duration is near optimal for reduction of amplitude of the somatosensory evoked potential The current densities per electrode were 5–11 mA/cm2 with a charge per pulse of 0.04–0.08 µC in humans with 15–20 electrodes on each superior surface and 10 electrodes on each posterior cerebellar surface.
Alterations in GABAA Receptor α2 Subunit mRNA Expression following Reproductive Experience in Rats
Authors: Byrnes Elizabeth M. , Lee Jong O. , Bridges Robert S.
Published: May 2007

Background/Aim: Reproductive experience (i.e., pregnancy and lactation) alters anxiety-like behavior. One neurotransmitter system that may mediate the effects of reproductive experience on anxiety-like behavior is γ-aminobutyric acid (GABA). The purpose of the current study was to determine whether reproductive experience alters the mRNA expression of selective GABAA receptor subunits in brain regions associated with anxiety-like behaviors. Methods: Brains were collected from age-matched nulliparous and primiparous female rats in either diestrus or proestrus, and the subunit mRNA expression was determined using real-time reverse transcription-polymerase chain reaction with Taqman®. Results: Increased α1 mRNA expression was found in proestrus within both medial preoptic area (MPOA) and medial amygdala (MeA) in nulliparous and primiparous females. The expression of α2 mRNA was also increased within the MPOA in proestrus in both nulliparous and primiparous females; however, within the MeA, an increased α2 mRNA expression in proestrus was only observed in nulliparous females, with primiparous females having a significantly reduced expression when compared to nulliparous controls. In addition, a significant increase in the expression of α2 mRNA expression was observed within the periaqueductal gray of reproductively experienced female rats. Conclusion: These results indicate that reproductive experience results in significant shifts in the expression of GABAA α2 mRNA expression in the MeA.
Distinct Architecture of Lymphatic Vessels Induced by Chimeric Vascular Endothelial Growth Factor-C/Vascular Endothelial Growth Factor Heparin-Binding Domain Fusion Proteins
Authors: Tammela Tuomas , He Yulong , Lyytikkä Johannes , Jeltsch Michael , Markkanen Johanna , Pajusola Katri , Ylä-Herttuala Seppo , Alitalo Kari
Published: May 2007

Vascular endothelial growth factor (VEGF)-C and VEGF-D are composed of the receptor-binding VEGF homology domain and a carboxy-terminal silk homology domain that requires proteolytic cleavage for growth factor activation. Here, we explored whether the C-terminal heparin-binding domain of the VEGF
165
or VEGF
189
isoform also containing neuropilin-binding sequences could substitute for the silk homology domain of VEGF-C. Such VEGF-C/VEGF–heparin-binding domain chimeras were produced and shown to activate VEGF-C receptors, and, when expressed in tissues via adenovirus or adeno-associated virus vectors, stimulated lymphangiogenesis in vivo. However, both chimeras induced a distinctly different pattern of lymphatic vessels when compared with VEGF-C. Whereas VEGF-C–induced vessels were initially a dense network of small diameter vessels, the lymphatic vessels induced by the chimeric growth factors tended to form directly along tissue borders, along basement membranes that are rich in heparan sulfate. For example, in skeletal muscle, the chimeras induced formation of lumenized lymphatic vessels more efficiently than wild-type VEGF-C. We conclude that the matrix-binding domain of VEGF can target VEGF-C activity to heparin-rich basement membrane structures. These properties may prove useful for tissue engineering and attempts to regenerate lymphatic vessels in lymphedema patients.
Acyclic Retinoid Inhibits Neointima Formation Through Retinoic Acid Receptor Beta-Induced Apoptosis
Authors: Kada Nanae , Suzuki Toru , Aizawa Kenichi , Matsumura Takayoshi , Ishibashi Naoto , Suzuki Naomi , Takeda Norifumi , Munemasa Yoshiko , Sawaki Daigo , Ishikawa Takashi , Nagai Ryozo
Published: May 2007

Objectives—

Acyclic retinoid (ACR) is a synthetic retinoid with a high safety profile that has been pursued with high expectations for therapeutic use in prevention (recurrence) and treatment of malignancies. With the objective of addressing the therapeutic potential in the cardiovasculature, namely neointima formation, effects of ACR on neointima formation and the involved mechanisms were investigated.

Methods and Results—

ACR was administered to cuff-injured mice which showed inhibition of neointima formation. Investigation of involved mechanisms at the cellular and molecular levels showed that ACR induces apoptosis of neointimal cells and this to be mediated by selective induction of retinoic-acid receptor β (RARβ) which shows growth inhibitory and proapoptotic effects on smooth muscle cells.

Conclusion—

We show that ACR inhibits neointima formation by inducing RARβ which in turn inhibits cell growth and induces apoptosis. The retinoid, ACR, may be potentially exploitable for treatment and prevention of neointima formation.
Expression of Human OSBP-Related Protein 1L in Macrophages Enhances Atherosclerotic Lesion Development in LDL Receptor–Deficient Mice
Authors: Yan Daoguang , Jauhiainen Matti , Hildebrand Reeni B. , Willems van Dijk Ko , Van Berkel Theo J.C. , Ehnholm Christian , Van Eck Miranda , Olkkonen Vesa M.
Published: May 2007

Objective—

The purpose of this study was to assess the role of macrophage OSBP-related protein 1L (ORP1L) in the development of atherosclerosis.

Methods and Results—

C57BL/6 mice overexpressing human ORP1L in macrophages driven by scavenger receptor A promoter were generated. Bone marrow (BM) of the mice was transplanted into LDLr
−/−
animals, and aortic root lesion area in the recipients was determined after Western-type diet feeding. The recipients of
ORP1L
BM displayed 2.1-fold increase (
P
<0.001) in lesion size as compared with recipients of wild-type littermate BM. Macrophages of the
ORP1L
BM recipients showed a decrease in
ABCG1
and
APOE
mRNAs and proteins, and an increase in
PLTP
message; also the plasma PLTP activity was elevated. The effect of ORP1L on cholesterol efflux was assessed using macrophages loaded with [
3
H]cholesterol oleate-acLDL or labeled with [
3
H]cholesterol. The
ORP1L
transgenic macrophages displayed 30% reduction (
P
<0.01) in cholesterol efflux to HDL
2
, but not to apoA-I. ORP1L was shown to bind 25- and 22(R)-hydroxycholesterol, identifying it as an oxysterol binding protein. Furthermore, ORP1L attenuated the response of
ABCG1
mRNA to 22(R)-hydroxycholesterol, the effect on
ABCA1
being less pronounced.

Conclusions—

The results demonstrate that macrophage ORP1L can act as a modulator of atherosclerotic lesion development and provide clues to the underlying mechanism.
Removal of Fkbp12/12.6 From Endothelial Ryanodine Receptors Leads to an Intracellular Calcium Leak and Endothelial Dysfunction
Authors: Long Cheng , Cook Leslie G. , Wu Gang-Yi , Mitchell Brett M.
Published: May 2007

Objectives—FK506BindingProtein 12 and its related isoform 12.6 (FKBP12/12.6) stabilize a closed state of intracellular Ca2+release channels (ryanodine receptors [RyRs]), and in myocytes removal of FKBP12/12.6 from RyRs alters intracellular Ca2+levels. The immunosuppressive drugs rapamycin and FK506 bind and displace FKBP12/12.6 from RyRs, and can also cause endothelial dysfunction and hypertension. We tested whether rapamycin and FK506 cause an intracellular Ca2+leak in endothelial cells and whether this affects endothelial function and blood pressure regulation.

Methods and Results—Rapamycin or FK506 concentration-dependently caused a Ca2+leak in isolated endothelial cells, decreased aortic NO production and endothelium-dependent dilation, and increased systolic blood pressure in control mice. Rapamycin or FK506 at 10 μmol/L abolished aortic NO production and endothelium-dependent dilation. Similar results were obtained in isolated endothelial cells and aortas from FKBP12.6−/−mice after displacement of FKBP12 with 1 μmol/L rapamycin or FK506. In hypertensive FKBP12.6−/−mice, systolic blood pressures were further elevated after treatment with either rapamycin or FK506. Blockade of the Ca2+leak with ryanodine normalized NO production and endothelium-dependent dilation.

Conclusions—Complete removal of FKBP12 and 12.6 from endothelial RyRs induces an intracellular Ca2+leak which may contribute to the pathogenesis of endothelial dysfunction and hypertension caused by rapamycin or FK506.
TNF-α Suppresses Prolyl-4-Hydroxylase α1 Expression via the ASK1–JNK–NonO Pathway
Authors: Zhang Cheng , Zhang Ming-Xiang , Shen Ying H. , Burks Jared K. , Zhang Yun , Wang Jian , LeMaire Scott A. , Yoshimura Koichi , Aoki Hiroki , Coselli Joseph S. , Wang Xing Li
Published: May 2007

Background—

Inflammation is known to contribute to the pathogenesis of vascular diseases in which arterial wall extracellular matrix (ECM) homeostasis is disrupted. Tumor necrosis factor-α (TNF-α), a pivotal cytokine that regulates ECM metabolism by increasing degradation and decreasing production of arterial collagens, is associated with vulnerable plaques and aortic aneurysms.

Methods and Results—

In the current study, we showed that, when administered in doses of 1 to 100 ng/mL, TNF-α dose-dependently downregulated the expression of prolyl-4-hydroxylase αI [P4Hα(I)]—the rate-limiting subunit for the P4H enzyme essential for procollagen hydroxylation, secretion, and deposition in primary human aortic smooth muscle cells (HASMCs). Using a progressive deletion cloning approach, we characterized the TNF-α–responsive element (TaRE) in the human P4Hα(I) promoter and found that a negative regulatory region at the position of −32 to +18bp is responsible for ≈80% of TNF-α–mediated suppression. Using oligonucleotide-based transcription factor pull-down method in which proteins were resolved in 1-D gel electrophoresis and identified using LC-MS/MS, we identified the NonO protein binds this region. When NonO expression silenced with specific siRNA, we found that 70% of the TNF-α–mediated P4Hα suppression was abolished, which appeared to be mediated by the ASK1-JNK pathway.

Conclusions—

Our findings define a novel molecular pathway for inflammation associated extracellular matrix dysregulation, which may account for atherosclerotic plaque rupture and aortic aneurysm formation. Further understanding of this pathway may facilitate development of novel therapeutics for vascular diseases.
Toll-Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity
Authors: Kim Francis , Pham Matilda , Luttrell Ian , Bannerman Douglas D. , Tupper Joan , Thaler Joshua , Hawn Thomas R. , Raines Elaine W. , Schwartz Michael W.
Published: May 2007

Vascular dysfunction is a major complication of metabolic disorders such as diabetes and obesity. The current studies were undertaken to determine whether inflammatory responses are activated in the vasculature of mice with diet-induced obesity, and if so, whether Toll-Like Receptor-4 (TLR4), a key mediator of innate immunity, contributes to these responses. Mice lacking TLR4 (TLR4
−/−
) and wild-type (WT) controls were fed either a low fat (LF) control diet or a diet high in saturated fat (HF) for 8 weeks. In response to HF feeding, both genotypes displayed similar increases of body weight, body fat content, and serum insulin and free fatty acid (FFA) levels compared with mice on a LF diet. In lysates of thoracic aorta from WT mice maintained on a HF diet, markers of vascular inflammation both upstream (IKKβ activity) and downstream of the transcriptional regulator, NF-κB (ICAM protein and IL-6 mRNA expression), were increased and this effect was associated with cellular insulin resistance and impaired insulin stimulation of eNOS. In contrast, vascular inflammation and impaired insulin responsiveness were not evident in aortic samples taken from TLR4
−/−
mice fed the same HF diet, despite comparable increases of body fat mass. Incubation of either aortic explants from WT mice or cultured human microvascular endothelial cells with the saturated FFA, palmitate (100 μmol/L), similarly activated IKKβ, inhibited insulin signal transduction and blocked insulin-stimulated NO production. Each of these effects was subsequently shown to be dependent on both TLR4 and NF-κB activation. These findings identify the TLR4 signaling pathway as a key mediator of the deleterious effects of palmitate on endothelial NO signaling, and are the first to document a key role for TLR4 in the mechanism whereby diet-induced obesity induces vascular inflammation and insulin resistance.
Transitions in Early Embryonic Atrioventricular Valvular Function Correspond With Changes in Cushion Biomechanics That Are Predictable by Tissue Composition
Authors: Butcher Jonathan T. , McQuinn Tim C. , Sedmera David , Turner Debi , Markwald Roger R.
Published: May 2007

Endocardial cushions are critical to maintain unidirectional blood flow under constantly increasing hemodynamic forces, but the interrelationship between endocardial cushion structure and the mechanics of atrioventricular junction function is poorly understood. Atrioventricular (AV) canal motions and blood velocities of embryonic chicks at Hamburger and Hamilton (HH) stages 17, 21, and 25 were quantified using ultrasonography. Similar to the embryonic zebrafish heart, the HH17 AV segment functions like a suction pump, with the cushions expanding in a wave during peak myocardial contraction and becoming undetectable during the relaxation phase. By HH25, the AV canal contributes almost nothing to the piston-like propulsion of blood, but the cushions function as stoppers apposing blood flow with near constant thickness. Using a custom built mesomechanical testing system, we quantified the nonlinear pseudoelastic biomechanics of developing AV cushions, and found that both AV cushions increased in effective modulus between HH17 and HH25. Enzymatic digestion of major structural constituent collagens or glycosaminoglycans resulted in distinctly different stress-strain curves suggestive of their individual contributions. Mixture theory using histologically determined volume fractions of cells, collagen, and glycosaminoglycans showed good prediction of cushion material properties regardless of stage and cushion position. These results have important implications in valvular development, as biomechanics may play a larger role in stimulating valvulogenic events than previously thought.
Deletion of LOX-1 Reduces Atherogenesis in LDLR Knockout Mice Fed High Cholesterol Diet
Authors: Mehta Jawahar L. , Sanada Nobuhito , Hu Chang Ping , Chen Jiawei , Dandapat Abhijit , Sugawara Fumiaki , Satoh Hiroo , Inoue Kazuhiko , Kawase Yosuke , Jishage Kou-ichi , Suzuki Hiroshi , Takeya Motohiro , Schnackenberg Laura , Beger Richard , Hermonat Paul L. , Thomas Maria , Sawamura Tatsuya
Published: May 2007

Atherosclerosis is associated with oxidative stress and inflammation, and upregulation of LOX-1, an endothelial receptor for oxidized LDL (oxLDL). Here, we describe generation of LOX-1 knockout (KO) mice in which binding of oxLDL to aortic endothelium was reduced and endothelium-dependent vasorelaxation preserved after treatment with oxLDL (
P
<0.01 versus wild-type mice). To address whether endothelial functional preservation might lead to reduction in atherogenesis, we crossed LOX-1 KO mice with LDLR KO mice and fed these mice 4% cholesterol/10% cocoa butter diet for 18 weeks. Atherosclerosis was found to cover 61±2% of aorta in the LDLR KO mice, but only 36±3% of aorta in the double KO mice. Luminal obstruction and intima thickness were significantly reduced in the double KO mice (versus LDLR KO mice). Expression of redox-sensitive NF-κB and the inflammatory marker CD68 in LDLR KO mice was increased (
P
<0.01 versus wild-type mice), but not in the double KO mice. On the other hand, antiinflammatory cytokine IL-10 expression and superoxide dismutase activity were low in the LDLR KO mice (
P
<0.01 versus wild-type mice), but not in the double KO mice. Endothelial nitric oxide synthase expression was also preserved in the double KO mice. The proinflammatory signal MAPK P38 was activated in the LDLR KO mice, and LOX-1 deletion reduced this signal. In conclusion, LOX-1 deletion sustains endothelial function leading to a reduction in atherogenesis in association with reduction in proinflammatory and prooxidant signals.