bluuebunny/crossref_metadata_2025 huggingface dataset:
Bexarotene (LGD1069, Targretin), a Selective Retinoid X Receptor Agonist, Prevents and Reverses Gemcitabine Resistance in NSCLC Cells by Modulating Gene Amplification
Authors: Tooker Patricia , Yen Wan-Ching , Ng Shi-Chung , Negro-Vilar Andrès , Hermann Thomas W.
Published: May 2007

Acquired drug resistance is a major obstacle in cancer therapy. As for many other drugs, this is also the case for gemcitabine, a nucleoside analogue with activity against non–small cell lung cancer (NSCLC). Here, we evaluate the ability of bexarotene to modulate the acquisition and maintenance of gemcitabine resistance in Calu3 NSCLC models. In the prevention model, Calu3 cells treated repeatedly with gemcitabine alone gradually developed resistance. However, with inclusion of bexarotene, the cells remained chemosensitive. RNA analysis showed a strong increase of rrm1 (ribonucleotide reductase M1) expression in the resistant cells (Calu3-GemR), a gene known to be involved in gemcitabine resistance. In addition, the expression of genes surrounding the chromosomal location of rrm1 was increased, suggesting that resistance was due to gene amplification at the chr11 p15.5 locus. Analysis of genomic DNA confirmed that the rrm1 gene copy number was increased over 10-fold. Correspondingly, fluorescence in situ hybridization analysis of metaphase chromosomes showed an intrachromosomal amplification of the rrm1 locus. In the therapeutic model, bexarotene gradually resensitized Calu3-GemR cells to gemcitabine, reaching parental drug sensitivity after 10 treatment cycles. This was associated with a loss in rrm1 amplification. Corresponding with the in vitro data, xenograft tumors generated from the resistant cells did not respond to gemcitabine but were growth inhibited when bexarotene was added to the cytotoxic agent. The data indicate that bexarotene can resensitize gemcitabine-resistant tumor cells by reversing gene amplification. This suggests that bexarotene may have clinical utility in cancers where drug resistance by gene amplification is a major obstacle to successful therapy. [Cancer Res 2007;67(9):4425–33]
Stroma-Derived Matrix Metalloproteinase (MMP)-2 Promotes Membrane Type 1-MMP–Dependent Tumor Growth in Mice
Authors: Taniwaki Kaori , Fukamachi Hiroshi , Komori Kiyoshi , Ohtake Yohei , Nonaka Takahiro , Sakamoto Takeharu , Shiomi Takayuki , Okada Yasunori , Itoh Takeshi , Itohara Shigeyoshi , Seiki Motoharu , Yana Ikuo
Published: May 2007

Matrix metalloproteinase-2 (MMP-2) is a stroma-derived MMP belonging to the type IV collagenase family. It is believed to mediate tumor cell behavior by degrading deposits of type IV collagen, a major component of the basement membrane. The membrane type 1-MMP (MT1-MMP) is a highly potent activator of MMP-2 and is expressed in many tumor and stromal cells. However, the roles played by stromal MMP-2 in tumor progression in vivo remain poorly understood. We established a colon epithelial cell line from an Mt1-mmp−/− mouse strain and transfected these cells with an inducible expression system for MT1-MMP (MT1rev cells). Following s.c. implantation into Mmp-2+/+ mice and induction of MT1-MMP expression, MT1rev cells grew rapidly, whereas they grew very slowly in Mmp-2−/− mice, even in the presence of MT1-MMP. This MT1-MMP–dependent tumor growth of MT1rev cells was enhanced in Mmp-2−/− mice as long as MMP-2 was supplied via transfection or coimplantation of MMP-2–positive fibroblasts. MT1rev cells cultured in vitro in a three-dimensional collagen gel matrix also required the MT1-MMP/MMP-2 axis for rapid proliferation. MT1rev cells deposit type IV collagen primarily at the cell-collagen interface, and these deposits seem scarce at sites of invasion and proliferation. These data suggest that cooperation between stroma-derived MMP-2 and tumor-derived MT1-MMP may play a role in tumor invasion and proliferation via remodeling of the tumor-associated basement membrane. To our knowledge, this is the first study demonstrating that MT1-MMP–dependent tumor growth in vivo requires stromal-derived MMP-2. It also suggests that MMP-2 represents a potential target for tumor therapeutics. [Cancer Res 2007;67(9):4311–9]
Rational Drug Redesign to Overcome Drug Resistance in Cancer Therapy: Imatinib Moving Target
Authors: Fernández Ariel , Sanguino Angela , Peng Zhenghong , Crespo Alejandro , Ozturk Eylem , Zhang Xi , Wang Shimei , Bornmann William , Lopez-Berestein Gabriel
Published: May 2007

Protein kinases are central targets for drug-based cancer treatment. To avoid functional impairment, the cell develops mechanisms of drug resistance, primarily based on adaptive mutations. Redesigning a drug to target a drug-resistant mutant kinase constitutes a therapeutic challenge. We approach the problem by redesigning the anticancer drug imatinib guided by local changes in interfacial de-wetting propensities of the C-Kit kinase target introduced by an imatinib-resistant mutation. The ligand is redesigned by sculpting the shifting hydration patterns of the target. The association with the modified ligand overcomes the mutation-driven destabilization of the induced fit. Consequently, the redesigned drug inhibits both mutant and wild-type kinase. The modeling effort is validated through molecular dynamics, test tube kinetic assays of downstream phosphorylation activity, high-throughput bacteriophage-display kinase screening, cellular proliferation assays, and cellular immunoblots. The inhibitor redesign reported delineates a molecular engineering paradigm to impair routes for drug resistance. [Cancer Res 2007;67(9):4028–33]
Thanatop: A Novel 5-Nitrofuran that Is a Highly Active, Cell-Permeable Inhibitor of Topoisomerase II
Authors: Polycarpou-Schwarz Maria , Müller Kerstin , Denger Stefanie , Riddell Andrew , Lewis Joe , Gannon Frank , Reid George
Published: May 2007

A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhibition of estrogen signaling in cells. The most potent nitrofuran discovered is ∼10-fold more active than etoposide phosphate, a topoisomerase II inhibitor in clinical use. The nitrofurans also inhibit topoisomerase I activity, with ∼20-fold less activity. Moreover, the nitrofurans, in contrast to etoposide, induce a profound cell cycle arrest in the G0-G1 phase of the cell cycle, do not induce double-stranded DNA breaks, are not substrates for multidrug resistance protein-1 export from the cell, and are amenable to synthetic development. In addition, the nitrofurans synergize with etoposide phosphate in cell killing. Clonogenic assays done on a panel of human tumors maintained ex vivo in nude mice show that the most active compound identified in the screen is selective against tumors compared with normal hematopoietic stem cells. However, this compound had only moderate activity in a mouse xenograft model. This novel class of topoisomerase II inhibitor may provide additional chemotherapeutic strategies for the development of cytotoxic agents with proven clinical utility. [Cancer Res 2007;67(9):4451–8]
p21 Loss Cooperates with INK4 Inactivation Facilitating Immortalization and Bcl-2–Mediated Anchorage-Independent Growth of Oncogene-Transduced Primary Mouse Fibroblasts
Authors: Carbone Christopher J. , Graña Xavier , Reddy E. Premkumar , Haines Dale S.
Published: May 2007

The INK4 and CIP cyclin-dependent kinase (Cdk) inhibitors (CKI) activate pocket protein function by suppressing Cdk4 and Cdk2, respectively. Although these inhibitors are lost in tumors, deletion of individual CKIs results in modest proliferation defects in murine models. We have evaluated cooperativity between loss of all INK4 family members (using cdk4r24c mutant alleles that confer resistant to INK4 inhibitors) and p21Waf1/Cip1 in senescence and transformation of mouse embryo fibroblasts (MEF). We show that mutant cdk4r24c and p21 loss cooperate in pRb inactivation and MEF immortalization. Our studies suggest that cdk4r24c mediates resistance to p15INK4B/p16INK4A that accumulates over passage, whereas loss of p21 suppresses hyperoxia-induced Cdk2 inhibition and pRb dephosphorylation on MEF explantation in culture. Although cdk4r24c and p21 loss cooperate in H-rasV12/c-myc–induced foci formation, they are insufficient for oncogene-induced anchorage-independent growth. Interestingly, p21−/−; cdk4r24c MEFs expressing H-rasV12 and c-myc display detachment-induced apoptosis and are transformed by c-myc, H-rasV12, and Bcl-2. We conclude that the INK4 family and p21 loss cooperate in promoting pRb inactivation, cell immortalization, and H-rasV12/c-myc–induced loss of contact inhibition. In addition, absence of pRb function renders H-rasV12 + c-myc–transduced fibroblasts prone to apoptosis when deprived of the extracellular matrix, and oncogene-induced anchorage-independent growth of pocket protein–deficient cells requires apoptotic suppression. [Cancer Res 2007;67(9):4130–7]
Paradoxes of the EphB4 Receptor in Cancer
Authors: Noren Nicole K. , Pasquale Elena B.
Published: May 2007

Recent findings have started to uncover the intriguing roles of the Eph family of receptor tyrosine kinases in normal epithelial cells and during oncogenic transformation. This review focuses on EphB4, an Eph receptor that has both tumor-suppressing and tumor-promoting activities in breast cancer. Understanding the multifaceted role of EphB4 in tumorigenesis may allow the development of new anticancer therapies. [Cancer Res 2007;67(9):3994–7]
Visuomotor Integration Is Compromised in Alzheimer’s Disease Patients Reaching for Remembered Targets
Authors: Tippett William J. , Krajewski Adam , Sergio Lauren E.
Published: May 2007

This study examined the ability of neurologically healthy individuals and individuals with Alzheimer’s disease (AD) to successfully complete procedures involving short-term spatial visuomotor memory tasks, and tasks involving increasingly complex visuomotor transformations. Participants made sliding finger movements over a clear touch-sensitive screen on two separate spatial planes (vertical and horizontal), to visually constant and remembered target positions. Significant main effects were observed between participant groups on reaction time and movement time measures. As well, significant changes in reaction time and movement time were observed within the patient group over the different of any experimental procedures. In addition, as task increased in complexity significant increases in errors were observed in the AD group. Overall, the results reveal that AD patients show substantial declines in their ability to process and integrate visual information to produce motor responses. Therefore, we believe that this psychophysical research provides further evidence that AD, even early stages of AD, can affect anatomical regions supporting vision for action.
Association of Tumor Necrosis Factor Polymorphisms with Guillain-Barré Syndrome
Authors: Zhang Jing , Dong Hui , Li Bin , Li Chun-yan , Guo Li
Published: May 2007

It has been reported that the tumor necrosis factor (TNF)α promoter polymorphism is associated with autoimmune disease and inflammatory disease. It has also been claimed that this polymorphism may affect TNFα expression. We investigated the TNFα –308 polymorphism and TNFα levels in 79 unrelated Chinese patients with Guillain-Barré syndrome (GBS) and 78 healthy controls using PCR-RFLP and ELISA assay. Patients with GBS were divided into 2 subgroups, acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), based on electrophysiological information. We found that the TNFα2 allele was associated with increased risk of GBS (OR = 1.876, 95% CI = 1.144–3.075, p = 0.008), particularly for AMAN, the main subtype (OR = 2.914, 95% CI = 1.412–6.015, p = 0.004), but there was no association between TNFα polymorphism and AIDP. We also found that carriers of the TNFα2 allele had significantly higher TNFα2 levels than TNFα1 homozygotes (p < 0.05). These data indicate that TNFα promoter polymorphism is responsible for susceptibility to GBS, especially to AMAN. The TNFα2 allele is associated with higher levels of TNFα.
Can We Talk about CD4+CD28– Lymphocytes as a Risk Factor for Ischemic Stroke?
Authors: Nowik M. , Nowacki P. , Grabarek J. , Drechsler H. , Białecka M. , Widecka K. , Stankiewicz J. , Safranow K.
Published: May 2007

Background: CD4+CD28– lymphocytes are implicated in the destabilization of atheromatous plaque, leading to acute coronary episodes. One may ask whether these cells play a similar role in ischemic stroke pathogenesis with an atherosclerotic background. Methods: Flow cytometry was applied to determine the percentage of CD4+CD28– lymphocytes in the peripheral blood of patients during the acute phase of their first ischemic stroke (group I) and in patients without a history of stroke but with two of the most important risk factors (hypertension, diabetes) for atherosclerosis-related ischemic stroke (group II). The results were compared with healthy controls. Results: The median percentages of CD4+CD28– lymphocytes in groups I and II did not differ significantly, but for each of these groups the percentage was higher than in the control group. The time of blood sampling from onset of stroke, presence of the ischemic focus in the CT brain scan and severity of neurological deficits did not correlate with the percentage of CD4+CD28– lymphocytes. Conclusions: We conclude that CD4+CD28– lymphocytes are implicated in mechanisms enhancing the risk of acute ischemic stroke and not a consequence of stroke.
Heterogeneity of Cognitive Dysfunction in Parkinson’s Disease: A Cohort Study
Authors: Verleden Stijn , Vingerhoets Guy , Santens Patrick
Published: May 2007

Aims: The aim of this study was to examine the heterogeneity of cognitive dysfunction in Parkinson’s disease (PD) and to evaluate the contribution of cognitive criteria to the diagnosis of dementia in PD. Methods: In a sample of 100 consecutive PD patients with motor fluctuations, an extensive neuropsychological test battery was administered. Each PD patient’s cognitive profile was then compared with current cognitive criteria for dementia in PD. Results: Principal component analysis of the major test variables resulted in three components: one concerned with memory/attention, one with visuospatial, and one with executive/motor functions. Eighteen percent of our cohort showed no significant impairment on either domain. Fifty-one percent showed impairment in one cognitive domain, most frequently in the executive/motor component (88%). Twenty-four percent performed below normal on two cognitive components, most often executive/motor and memory/attention deficits (96%), and only 7% of our cohort had significant impairment on each derived cognitive component. Depending on the used criteria, 10–30% percent of our cohort could be categorized as PD patients with dementia. Conclusions: Future guidelines for a uniform diagnosis of dementia in PD are needed for clinical use and therapeutic management.
Platybasia and Basilar Invagination
Authors: Pearce J.M.S.
Published: May 2007

Descriptions of the flattening (platybasia) of the skull base and the upward displacement(impression) of the basilar and condylar portions of the occipitalbone by the upper cervical spine date to the late 18th and early 19th centuries. Anatomical measurements to display these abnormalities were begun in 1865, but the full clinical significance was not appreciated until Homen’s work in 1901. Subsequent refinement of radiology facilitated diagnosis and the later advent of surgical treatment.
Possible Modes of Action of Extradural Electrical Stimulation on the Spinal Cord
Authors: Phillips Charles G.
Published: May 2007

Analysis of the actions of electric currents on excitable membranes has contributed greatly to our biophysical understanding of the initiation and transmission of impulses in nerve and muscle. The use of electrical stimulation in trying to unravel the complex structure and to understand the integrative properties of the central nervous system (CNS), however, raises problems of a different order. This is true of the application of electrical stimuli to mixed populations of axons in peripheral nerves in attempts to discover the central actions of inputs from the different receptive fields, from skin, for example, or muscle or joint. But the most complex problems of all are those raised by the application of electrical stimuli to the CNS itself, whether to try to find out how it works, or to try to relieve a patient''s disabilities. We would like to be able to specify, for any particular configuration of external electrodes, which populations of neurones and axons will be excited by virtue of appropriate orientation with respect to lines of current flowing cathodally within the non-isotropic conducting medium of the CNS. We would also like to know the quantities and locations of the brief excitatory and inhibitory synaptic actions, and the longer-term ''modulating'' actions, which they exert at nearby and remote areas of the brain and spinal cord. In man, much could be accomplished by attentive neurological examination, comparing sensory, motor and autonomic functions in the presence and absence of chronic stimulation, and correlating particular physiological effects with alterations of particular symptoms. Such examination would invoke all the technical resources of clinical neurophysiology. Direct evidence of the stimulation of particular spinal pathways and neurones, and of the distribution of remote excitatory and inhibitory effects, could be obtained only by multiple electrical recordings from brain and cord in animal experiments.
Dorsal Column Stimulation in Multiple Sclerosis: Effects on Bladder, Leg Blood Flow and Peptides
Authors: Hawkes C.H. , Fawcett D. , Cooke E.D. , Emson P.C. , Paul E.A. , Bowcock S.A.
Published: May 2007

9 patients with bladder disorder secondary to multiple sclerosis (MS) were treated by dorsal column stimulation (DCS). Detailed urodynamic tests were performed and leg blood flow was assessed on repeated occasions. Cerebrospinal fluid (CSF) met-enkephalin levels were estimated before and during DCS. The chief effect of DCS was improved urinary flow associated with reduced sphincter tone and lessened detrusor instability maximal at the 6th or 7th day of continuous stimulation. Considerable fluctuation in leg blood flow occurred unrelated to activation of the stimulator. No obvious change in CSF met-enkephalin levels took place, but it is suspected that the mode of action of DCS in via certain peptide hormones.
Treatment of Patients with Degenerative Diseases of the Central Nervous System by Electrical Stimulation of the Spinal Cord
Authors: Dooley Donald M. , Nisonson Ian
Published: May 2007

Patients with dystonia, spinocerebellar and cerebellar ataxia and spasmodic torticollis have a reasonable chance of being significantly aided in their control of motor function and neurogenic bladder by electrical stimulation of the cervical or thoracic spinal cord. This mode of therapy has the advantages that it is not destructive of neurological tissue, effects can be varied by altering the intensity and rate of the stimulus and preliminary testing with externalization of the electrodes is predictive of the effects of chronic stimulation.
Psychological Effects of Spinal Cord Stimulation: Preliminary Findings
Authors: Levita Eric , Rilan Manuel , Waltz Joseph M.
Published: May 2007

22 patients undergoing spinal cord stimulation (SCS) were studied for a period ranging from 4 to 6 weeks following initiation of treatment. SCS did not alter cognitive, perceptual or visuomotor efficiency. Affective changes involved most frequently were (1) mood elevation and reduced depression, (2) increased energy and activation, and (3) decreased anxiety or tension.
Indirect Spinal Cord Stimulation
Authors: Vodovnik Lojze
Published: May 2007

Some clinical results of the therapeutic effects of functional electrical stimulation (FES) are presented. Based on these data a model of the therapeutic effects of indirect spinal cord stimulation is proposed, as well as a hypothesis regarding the selective and beneficial effects of an apparently diffused and nonspecific stimulation. Further investigations should elucidate mechanisms which are common to direct and indirect spinal cord stimulation, as well as mechanisms which separate spinal cord stimulation from FES.
Quantification and Documentation of Changes Produced by Spinal Cord Stimulation
Authors: Struppler Albrecht , Struppler Elisabeth
Published: May 2007

In spastic patients suffering from spastic paresis on one side the degree of spasticity on the background of isometric innervation was investigated with a new self-constructed torque motor. It offers the opportunity to analyze how external forces can be compensated automatically by reflex or reaction. In spastic patients M1, M2 and M3 were compared with the responses of the nonaffected normal side as a control. The effects of diazepam and baclofen are analyzed with this new technique.
Underlying Mechanisms of the Effects of Spinal Cord Stimulation in Motor Disorders
Authors: Dimitrijevic M.R. , Faganel J. , Young R.R.
Published: May 2007

Possible underlying neurophysiological mechanisms of spinal cord stimulation in the modification of motor disorders were discussed by scientists working in research on motor control mechanisms. Changes of motor unit properties in upper motoneuron lesions were reviewed, the role of proprioceptive input and long-loop reflexes in motor control was discussed, analysis of ramp and ballistic movements in motor control was presented, and some aspects of neural control of locomotion were reviewed. Some physiological considerations of the influence of electrical stimulation on various neural functions were given and the conclusion was reached that, at present, no definitive models of the action of spinal cord stimulation are available.
Neural Control of Gait: Clinical Neurophysiological Aspects
Authors: Dimitrijevic M.R. , Larsson L.-E.
Published: May 2007

From the three essential mechanisms in locomotion, the antigravity, equilibrium and stepping mechanisms, only the latter is specific for gait. The spinal cord is considered to be a central pattern generator in experimental animals and is under the influence of different afferent sources and descending impulses. In clinical practice locomotor mechanisms can be modified at peripheral levels, as with functional electrical stimulation of peripheral nerves, and at the spinal cord, as in spinal cord stimulation, and theoretically also at midbrain and subthalamic locomotor areas. The importance of the spinal cord pattern generator in spinal cord injured patients is discussed. The role of postural mechanisms in locomotion is emphasized.
Technical Factors Important to Dorsal Column Stimulation
Authors: Davis Ross , Gray Edward
Published: May 2007

A series of 101 patients with weakened neurological conditions (including multiple sclerosis and other demyelinating diseases) were augmented with dorsal column stimulation (DCS) over a 5½-year period. 65 patients were implanted with an RF-linked system while 36 had a fully implantable programmable stimulator inserted. 20% failure occurred in the radio receiver series while none occurred in the latter, except for routine battery depletion. After 5 years, 23% of the patients using the RF system continued to use DCS, while after 4 years of using the fully implantable units, 81% of the patients continued to use DCS. Electrode displacement occurred in 27 patients, with breakage in a further 6 patients early in the series. Cathodal stimulation is more efficient than anodal stimulation when compared in 21 patients undergoing DCS.
Hypothetical Role of Long-Loop Reflex Pathways
Authors: Delwaide P.J. , Toulouse P. , Crenna P.
Published: May 2007

It is nowadays well known that there are reflex loops starting in the spinal cord, relaying in various supraspinal structures and descending back to the cord. These long-loops regulate motor responses and work in cooperation with segmental mono- and polysynaptic reflexes. The role of certain well-documented long-loop reflexes is reviewed. The existence of additional long-loop reflexes is hypothetized and preliminary results supporting this view are presented. In discussing the mode of action of spinal cord stimulation, the various ascending and descending pathways involved in long-loop regulation of motricity are to be taken into account.
Stimulation of the Spinal Neuraxis by Biocompatible Electrical Current in the Human
Authors: LeRoy P.L.
Published: May 2007

A 5-year retrospective study shows that stimulation of the neuraxis by biocompatible on-demand electrical energy systems is an effective alternative in the management of chronic organic regional pain syndromes. The clinical criteria of improved sense of well-being – reduction of drug intake and increase in activities of daily living – were employed to show that 50% of selected patients reported improvement in 60% of the cases in which stimulation-induced hypalgesia (SIH) was present. There is no apparent significant difference between mono- and bipolar electrical systems. There was no surgical mortality in the series. Complications of electrode migration (6%), rejection syndrome (14%), infection (6%) and unknown causes (8%) did present technical problems that are being resolved. Granulation tissue, apparently stimulated by electrical energy, suggests application in the healing processes. The existence of a variable response neuronal adaptation system is suggested in some patients by the drop in stimulation efficacy after long-term stimulation of fully implanted systems. Challenge of SIH by antagonist naloxone produced variable responses in cooperative patients. The soporific effect seen with transcutaneous electrical nerve stimulation reported in 40% of cases is not seen with the fully implanted epidural systems, despite the use of similar on-demand pulse generators. Biocompatible electrical stimulation of the spinal neuroaxis holds promise as a management modality for highly selected human patients with chronic pain syndromes.
Multi-Lead Spinal Cord Stimulation for Control of Motor Disorders
Authors: Waltz Joseph M. , Reynolds Leslie O. , Riklan Manuel
Published: May 2007

This report presents observations in 160 patients undergoing chronic spinal cord stimulation for various disorders of the motor system and compares the results obtained using older conventional two-electrode bipolar stimulation with a newly developed four-electrode multiple level system. Improvement was noted in 84% of the 75 patients with cerebral palsy, 67% of the 42 patients with dystonia, 62% of the 21 patients with torticollis and 73% of the 22 patients with post-traumatic neurologic loss. Significant improvements were noted when comparing the two-electrode system with the new multiple level electrode. Marked to moderately improved patients increased from 57 to 84% in cerebral palsy, from 44 to 82% in dystonia, from 53 to 75% in torticollis and from 53 to 80% in posttraumatic neurologic conditions. There was a corresponding marked drop in unimproved patients in each condition.
The Basal Ganglia-Circa 1982 (Part 1 of 2)
Authors: Mehler William R.
Published: May 2007

Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's [88] proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's [72] more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.
Touch-Evoked Thalamic Cellular Activity
Authors: Hardy Tyrone L. , Bertrand B. , Thompson C.J.
Published: May 2007

With the aid of a computer graphic technique, data gathered from exploratory diencephalic recordings in 130 stereotactic operative procedures are presented to show the variable position of the anterior border of somesthetic SI (touch-evoked) thalamus and the somatotopographic distribution of responses.
Bilateral Improvement in Voluntary Movement after Unilateral Diencephalic Lesions for Parkinsonism
Authors: Meyer Carl H.A.
Published: May 2007

In 14 patients with parkinsonism a unilateral ablation at the lower border of the ventrolateral thalamus relieved tremor and rigidity in the contralateral arm but not in the ipsilateral arm. Voluntary movement improved in both arms for three single-handed tasks, each involving the proximal and distal parts of the limb. For one task (a ballistic drawing movement) the postoperative change in one arm was correlated with that in the other arm. The lesion also improved repetitive voluntary movement of the fingers, but only in the contralateral hand.
Cortical-Evoked Responses Before and After Percutaneous Thermocoagulation of the Gasserian Ganglion. Preliminary Report
Authors: Salar G. , Job I. , Mingrino S.
Published: May 2007

Percutaneous thermocoagulation of the Gasserian ganglion allows a good preservation of facial touch sensation with a complete and immediate regression of the symptomatology in a majority of cases. Neurophysiological bases are the peculiar resistance to the thermal lesion of the large myelinated fibers compared to the relatively smaller fibers. The study of the cortical-evoked responses before and after surgery suggests that the afferent volley travels in preference along these large myelinated fibers.
Somatosensory Evoked Potentials in Deep Hypothermia
Authors: Stejskal L. , Trávníček V. , Šourek K. , Kredba J.
Published: May 2007

Treatment with general anesthesia (neuroleptanalgesia) and deep hypothermia was performed on 8 patients suffering from epilepsy. The body temperature was decreased to 29 °C and the temperature in the brain ventricles to 16 °C. Somatosensory evoked potentials were recorded. Increase in latency of all waves was observed, and it was noted that the more distant the wave, the higher the increase in latency. Statistical values are given for N1, N2 and N3. A parallel decrease in the amplitudes of all components of the somatosensory evoked potential was also present.
Position and Organization of Thalamic Cellular Activity during Diencephalic Recording
Authors: Hardy Tyrone L. , Bertrand Gilles , Thompson C.J.
Published: May 2007

With the aid of a computer graphic display technique, data gathered from exploratory diencephalic recordings in 130 stereotactic operative procedures are presented to show the differing topographical distribution of ''joint''- and ''muscle''-evoked cellular activity. In addition, the variable position of these responses in relation to common diencephalic landmarks is presented. Our findings indicate that response points lie in a sickle-shaped zone 14–19 mm lateral to the midline and 2–11 mm posterior to the midcommissural plane. This area correlates closely with the findings of others on the thalamic zone of 1A afferent projections and agrees with the anatomical position of the nucleus ventralis intermedius as plotted by others. When the response points are plotted against a common posterior commissure, a more compact grouping is obtained and ''muscle''- and ''joint''-evoked responses are noted to separate into different zones, with ''muscle'' responses positioned slightly anterior and inferior to those for ''joint''. Somatotopographically, face responses were positioned posteriomedially and leg responses anterolaterally.
The Function of the Human Cerebellum Studied by Evoked Potentials and Motor Reactions
Authors: Tóth S. , Vajda J. , Sólyom A.
Published: May 2007

The authors investigated the cerebellar function of patients with chronic implanted electrodes. The investigations were carried out using elicited compulsion events – evoked potentials and motor reactions – in different functional motor states, i.e., rest and contraction. The compulsion events are the result of motor control processes which eliminate the transient effect of stimuli. In connection with the cerebellum, these motor control processes in some ways mirror the function of the cerebellum. The evoked potentials recorded in the cerebellum have specific features and specific functional dependence as well. On stimulation of the cerebellum, the first effect on motor activity is always inhibitory. Altering the cerebellar function by high frequency stimulation appears to cause cerebellar symptoms such as hypotonia and ataxia.
Intermittent Decortication and Progressive Hyperthermia, Hypertension and Tachycardia following Methylglucamine Iothalamate Ventriculogram
Authors: Papadakis Nikolas , Mark Vernon H.
Published: May 2007

A case of intermittent decortication and progressive hyperthermia, hypertension and tachycardia is reported in connection with the use of methylglucamine iothalamate as an agent for ventriculography in a stereotactic procedure.
Topography of 'Bilateral-Movement-Evoked' Thalamic Cellular Activity Found during Diencephalic Recording
Authors: Hardy Tyrone L. , Bertrand Gilles , Thompson C.J.
Published: May 2007

With the aid of a computer graphic technique, data gathered from exploratory diencephalic recording in 130 stereotactic procedures are presented to show the topography of ‘bilateral-movement-evoked’ thalamic cellular activity. Thalamic cells responding to bilateral voluntary extremity movement were found to occupy a thalamic zone rostral to the zone for ‘muscle’- and ‘joint’-evoked thalamic cellular activity.
Stereotactic Fields of Forel Interruption for Intractable Epilepsy
Authors: Ramani S. Venkat , Yap Jesse C. , Gumnit Robert J.
Published: May 2007

Bilateral stereotactic fields of Forel surgery was carried out in 6 adults with chronic intractable epilepsy associated with multifocal EEG abnormalities. During an average 40 months follow-up, a significant reduction in the frequency of generalized tonic-clonic seizures was noted in 4 patients. Complex partial seizures in 3 patients and akinetic-myoclonic seizures in 1 did not respond to surgery. Neuropsychological testing revealed a mild to moderate postoperative cognitive decline in 4 patients. Fields of Forel surgery, while partially effective in generalized tonic clonic seizures, appears justified only in patients with such severe preexisting cognitive deficits, that the benefits of seizure control definitely outweigh the risk of further cognitive decline.
Long-Term Follow-Up Study after Pulvinotomy for Intractable Pain
Authors: Yoshii N. , Mizokami T. , Ushikubo T. , Kuramitsu T. , Fukuda S.
Published: May 2007

Pulvinotomy was performed on 42 cases with intractable pain. 19 cases survived for more than 1 year, the results were classified as follows: 4 were excellent, 4 good, 5 fair, and 4 were poor. The effects of the operation are discussed based on the disease. 2 cases, who survived for more than 1 year, suffered from the pain due to infiltration or metastasis of cancer, they died 22 and 14 months after the operation, respectively, but they had no intractable pain during the year before death. 14 cases who underwent CVD survived for more than 1 year. Results of the operation were as follows: 3 were excellent; 4 good; 4 fair, and 4 were poor. These cases were followed up for 3–10 years and the average was about 5 years. After more than 1 year, 2 cases with atypical facial pain were considered as being either fair or poor, one (fair case) of whom still does routine housework and is not drug dependent. A case of causalgia has been free from pain for 5 years after the operation.
Parafascicular-Center Median Nuclei Stimulation for Intractable Pain and Dyskinesia (Painful-Dyskinesia)
Authors: Andy O.J.
Published: May 2007

Medial thalamus stimulation was used to treat chronic intractable pain associated with dyskinesia. Relief from both the pain and the motor disorder occurred concomitantly. However, maximum pain reduction was attained at a relatively faster rate than maximum reduction from the motor disability. It is postulated that pathologic changes in the center median nucleus secondary to lenticulostriate-internal capsular lesions account, in part, for both the pain and the dyskinesia. Electrical stimulation of the center mediann parafascicular nuclear complex presumably simultaneously activates both the neurohumeral and tertiary sensory pain inhibitory systems for pain control, and the suprasegmental gamma system for motor control.
Stereotactic Hypophysectomy for Intractable Pain Secondary to Metastatic Prostate Carcinoma
Authors: Moser Richard P. , Yap Jesse C. , Fraley Elwin E.
Published: May 2007

Stereotactic radiofrequency transfrontal hypophysectomy was carried out in 7 patients with osseous metastasis from prostatic carcinoma resulting in intractable pain. 86% experienced significant pain relief with 5 of 7 demonstrating marked decrease in medication requirement and improved level of function. The procedure was done under local anesthesia only with no mortality and minimal morbidity. Total destruction of the pituitary gland and the development of diabetes insipidus were shown not to be necessary conditions for pain relief.
Technical and Clinical Aspects of CT-Directed Stereotaxis
Authors: Roberts Theodore S. , Brown R.
Published: May 2007

A system has been developed for using computed tomography to direct stereotactic neurosurgical procedures. This system operates with many commercially available CT body scanners and does not require any modification to be made to either the scanner or its computer software. The use of this system does not require rigid fixation of the patient to the scanner nor meticulous patient positioning in the scanner.
A Computerized Microstereotactic Method to Approach, 3-DimensionaIIy Reconstruct, Remove and Adjuvantly Treat Small CNS Lesions
Authors: Jacques Skip , Shelden C. Hunter , McCann Gilbert D.
Published: May 2007

The authors update a novel method recently utilized in humans with various CNS pathology for stereotactic localization, removal, and adjuvant therapy of small CNS lesions using additional computer processing of the data from a GE 8800 CT Scanner. Multiple computer algorithms developed at Cal Tech enhance regions of interest by filtering, magnifying, color-coding and 3-dimensional reconstruction based on routine CT scans. This stereotactic approach is calculated by the computer and coordinates are mated to a modified head fixation system; small lesions can be removed with the apparatus described herein under direct binocular vision with minimal tissue damage. This technique may offer the possibility of successful secondary application of adjuvant therapy to, particularly, a CNS glioma site.
Stereotactic Treatment of Brain Lesions
Authors: Mundinger F. , Ostertag Ch.B. , Birg W. , Weigel K.
Published: May 2007

Integrating CT imaging techniques into stereotactic procedures makes it easy to puncture cysts, take biopsies from neoplastic and nonneoplastic lesions, and place radioactive material in tumors at exact and reproducible sites. A stereotactic program of interstitial radiotherapy in deep-seated brain tumors has been applied in 326 cases as of December 31, 1979 (270 cases using iridium-192 and 56 cases using iodine-125). The use of iodine-125 is now favored since it requires less radiation protection due to its soft 28–35 keV radiation; at the same time, however, it possesses a comparable half life of 60 days. In 126 cases, stereotactic biopsy was used exclusively for diagnostic purposes followed by open craniotomy or conventional radiation. Cystic brain tumors (i.e., craniopharyngiomas and cystic low grade gliomas) were permanently drained by insertion of Rickham reservoir catheters in 61 cases. Stereotactic ventriculocisternostomies were carried out in cases of hydrocephalus and drainage of suprasellar arachnoid cysts was performed in 15 cases. A simple method of projecting CT images onto stereotactic X-ray pictures provides an exact mapping of lesions within the actual stereotactic brain space. The results of this series of patients strongly suggest that exploratory craniotomies and free-hand punctures can no longer be advocated. No radiation treatment should be considered without histological confirmation. The more clearly the volume of a tumor can be defined, the more favorable the results of interstitial irradiation in otherwise unresectable tumors.
Stereotactic Aspiration of Deep Cerebral Abscesses after CT-Directed Labeling
Authors: Walsh P.R. , Larson S.J. , Rytel M.W. , Maiman D.J.
Published: May 2007

Multiple, deep cerebral abscesses were treated in 2 patients by stereotactic aspiration after CT-guided needle labeling of single cavities. Separation of labeling from stereotactic manipulations avoids CT artifact generated by standard frame components; the technique will, therefore, accommodate most stereotactic instruments in current use. Alignment of CT and stereotactic coordinates hinged upon coidentification of the Pantopaque-labeled cavity on CT scans and on routine skull films with the stereotactic frame in place. Proximity of the label to targets eliminated the need for special head fixation or complex baseline correction.
A Method for Stereotactic Laser Microsurgery in the Treatment of Deep-Seated CNS Neoplasms
Authors: Kelly Patrick J. , Alker Jr. George J.
Published: May 2007

Intracranial tumors are reconstructed in stereotactic space by means of computerized axial tomographic data. The intracranial tumor is operated on with the patient in the stereotactic frame using a carbon dioxide laser to approach the lesion and vaporize it. Ultimately, a gas-filled cavity results which can be monitored on AP and lateral radiographs. Vaporization continues until the cavity produced is superimposable on the coronal and sagittal CT reconstruction. 2 cases treated by this method are presented.
DNA Distribution in Various Parts of Malignant Gliomas Assayed on Stereotactic Biopsies
Authors: Boëthius Jörgen , Bergstrand Gustaf , Collins V. Peter , Edner Göran , Tribukait Bernhard
Published: May 2007

The study concerns the relation between the computerized tomogram, histopathology and DNA distribution in gliomas. The investigation was performed on stereotactic biopsies, which enabled the comparison to be made on a point-to-point basis. No clear-cut relation was found between histopathological grading and DNA distribution. In 1 patient diploid and aneuploid tissue was found in different parts of the tumor. In this case the difference in ploidy was mirrored by differences in histopathological grading and gross morphology as indicated by the CT scan.
Importance of Microstereoencephalotomy for Tremor Alleviation
Authors: Narabayashi Hirotaro , Ohye Chihiro
Published: May 2007

Application of the microelectrode technique in human stereotactic surgery, which is especially important for tremor control, is now routine for the procedure in our surgical theater. Neurons responsible for tremor generation can very delicately and exactly be identified within the ventralis intermedius nucleus (Vim) of the thalamus, which automatically determines the location of the minimum required thermocoagulation lesion to abolish tremor. Neurons with rhythmic burst discharges, which are synchronus in phase to the peripheral tremor, are organized in delicate somatotopic fashion within the Vim. Electrical stimulation of the neuron area through this microelectrode usually inhibits tremor of the corresponding area and a small thermocoagulation lesion, usually 3 mm in diameter, permanently abolishes tremor. These three findings, i.e., existence of rhythmic bursts, effect of the stimulation and surgical lesion, are the same in parkinsonian tremor, postural tremor and intention tremor. Physiological interpretation of different types of tremor will be proposed. In the cases of idiopathic neck tremor, a single Vim neuron corresponded to four neck muscles, i.e., bilateral sternocleidomastoid muscle (SCM) and bilateral posterior neck muscles, and most markedly to the controlateral posterior neck muscle and the ipsilateral SCM. Instrumentation of microstereoencephalotomy is also explained.
Reversibility of Chronic Neurologic Deficits. Some Effects of Electrical Stimulation of the Thalamus and Internal Capsule in Man
Authors: Cooper I.S. , Upton A.R.M. , Amin I.
Published: May 2007

Stimulation of the thalamus and internal capsule with Medtronic® deep brain stimulation electrodes produced improvement in pain, hemiparesis, dystonia, torticollis, tremor, speech impairment and epilepsy. Stimulation at voltages above or below clinically effective levels (e.g., 6 V, 0.3 ms, 74 Hz) resulted in a loss of clinical efficacy. Somatosensory evoked responses (short and long latency) and depth electrode recordings were helpful in localisation and ‘biocalibration’ of electrical stimulation.
Long Term Cognitive Effects of Stereotactic Thalamotomy on Non-Parkinsonian Dyskinetic Patients
Authors: Blumetti A.E. , Modesti L.M.
Published: May 2007

Pre- and postoperative neuropsychological evaluation focusing on processing, memory, attentional and emotional deficits was performed on 10 non-parkinsonian dyskinetic patients undergoing single radiofrequency ventralateral (VL) unilateral thalamotomy. Patients carried a diagnosis of either familial tremor or multiple sclerosis and it was found that only in the cases of familial tremor was there no residual loss on long-term evaluation with consistent improvement post-operatively.
Microelectrode Recording for the Somatotopic Placement of Stereotactic Thalamic Lesions in the Treatment of Parkinsonian and Cerebellar Intention Tremor
Authors: Kelly Patrick J.
Published: May 2007

Patients with parkinsonian tremor and rigidity and cerebellar intention tremor can be effectively treated with thalamic lesions provided that an accurate neurophysiologic method is employed to compensate for individual spatial variability of subcortical structures. The method described employs a technique of microelectrode recording in which the homuncular organization in ventralis posterior is explored and gives information as to the ideal laterality of lateral thalamic nuclear mass lesions for the treatment of tremor. This procedure has been used in 11 patients, 9 with Parkinson''s disease and 2 with cerebellar intention tremor with good results and no complications to date.
Experimental Studies on Therapeutic Effect of Electrical Stimulation of the Brain on Muscular Hypertonus
Authors: Fujita Shigekiyo
Published: May 2007

Possible effective sites in the central nervous system for therapeutic electrical stimulation in muscular hypertonus are presented. The tonic vibration reflex (TVR) was used as a suitable model of a hypertonic muscular mechanism. Using cats, vibration of 225 Hz was applied to the tendon of the gastrocnemius and soleus muscles. During TVR, stimuli of 200 Hz were applied at various sites within the brain. Results showed that stimulation of the contralateral precruciate cortex, the medial part of the internal capsule, the ventralis anterior nucleus of the thalamus, and the ipsilateral anterior lobe of the cerebellum produced an intense inhibitory effect on TVR,but no significant effect by stimulation alone. Therefore, it is suggested that stimulation of these structures should be suitable for clinical application.