PubMed Health⌕ Search

Biomedical subjects

G T Gillies

Publications and source records attributed to G T Gillies.

At least 19 recordsLinked to original sources
PubMed2001

Static magnetic fields for treatment of fibromyalgia: a randomized controlled trial.

OBJECTIVE: To test effectiveness of static magnetic fields of two different configurations, produced by magnetic sleep pads, as adjunctive therapies in decreasing patient pain perception and improving functional status in individuals with fibromyalgia. DESIGN: Randomized, placebo-controlled, 6-month trial conducted from November 1997 through December 1998. SETTING AND SUBJECTS: Adults who met the 1990 American College of Rheumatology criteria for fibromyalgia were recruited through clinical referral and media announcements and evaluated at a university-based clinic. INTERVENTIONS: Subjects in Functional Pad A group used a pad for 6 months that provided whole-body exposure to a low, uniform static magnetic field of negative polarity. Subjects in the Functional Pad B group used a pad for 6 months that exposed them to a low static magnetic field that varied spatially and in polarity. Subjects in two Sham groups used pads that were identical in appearance and texture to the functional pads but contained inactive magnets; these groups were combined for analysis. Subjects in the Usual Care group continued with their established treatment regimens. OUTCOME MEASURES: Primary outcomes were the change scores at 6 months in the following measures: functional status (Fibromyalgia Impact Questionnaire), pain intensity ratings, tender point count, and a tender point pain intensity score. RESULTS: There was a significant difference among groups in pain intensity ratings (p = 0.03), with Functional Pad A group showing the greatest reduction from baseline at 6 months. All four groups showed a decline in number of tender points, but differences among the groups were not significant (p = 0.72). The functional pad groups showed the largest decline in total tender point pain intensity, but overall differences were not significant (p = 0.25). Improvement in functional status was greatest in the functional pad groups, but differences among groups were not significant (p = 0.23). CONCLUSIONS: Although the functional pad groups showed improvements in functional status, pain intensity level, tender point count, and tender point intensity after 6 months of treatment, with the exception of pain intensity level these improvements did not differ significantly from changes in the Sham group or in the Usual Care group.

Adolescent↗
PubMed2001

Quantitative three-dimensional analysis and diffusion modeling of oligonucleotide concentrations after direct intraparenchymal brain infusion.

We compared quantitative experimental results on the diffusion of 35S-labeled phosphorothioate oligonucleotide (PS-ODN) after intraparenchymal infusion in rat brain, with the distributions predicted by Fick's second law of diffusion. Fischer 344 rats underwent identical intracerebral infusions of 36S-PS-ODN. After 0, 5, 11, 23, and 47 h, groups of animals were sacrificed and sequential brain cryosections subjected to autoradiography. The resulting experimental data were compared to the predicted distributions, for estimation of the apparent free diffusion coefficient, D*. Volumes of distribution and total content of 36 S-PS-ODN in the parenchyma were also computed, to monitor loss of total material. The values for D* were within the expected range for the 21-mer PS-ODN used, but a progressive decrease in D* over time was noted. The model requires D* to remain constant and, thus, does not adequately explain the spread of 35S-PS-ODN following infusion. The progressive slowing of spread over time suggests that at later time points, 35S-PS-ODN may be fixed by tissue binding or cellular uptake in the brain. Loss of material via vascular and CSF clearance may also contribute to the lack of fit. Our results highlight issues to be addressed in the modeling and experimental design of the intraparenchymal infusion process.

Algorithms↗
PubMed2001

Minimally invasive procedures. Advances in image-guided delivery of drug and cell therapies into the central nervous system.

Image-guided transparenchymal delivery of drugs is an emerging neurosurgical modality that holds the promise of delivering various agents directly across the blood-brain barrier. Potential large-scale applications for convection-enhanced delivery of drugs through the interstitial space include the delivery of chemotherapeutic agents and gene therapy vectors for the treatment of brain tumors and the delivery of neurotrophic factors and neurotransmitters for the treatment of neurodegenerative disorders. The related technique of direct intraparenchymal injection of cells provides a means for transplanting neural stem cells into the brain for the treatment of degenerative diseases. Significant advances in catheter design, infusion strategies, and imaging technology have brought these procedures into the mainstream of human clinical testing, with clinical applications potentially on the near horizon.

Brain Neoplasms↗
PubMed2001

Cost-efficacy of MR-guided neurointerventions.

This article summarizes the available data on the cost-efficacy of interventional MR imaging and discusses its potential future role in the diagnosis and management of neurologic diseases and disorders.

Humans↗
PubMed2000

Determination of intracranial tumor volumes in a rodent brain using magnetic resonance imaging, Evans blue, and histology: a comparative study.

The measurement of tumor volumes is a practical and objective method of assessing the efficacy of a therapeutic agent. However, the relative accuracy of different methods of assessing tumor volume has been unclear. Using T1-weighted, gadolinium-enhanced magnetic resonance Imaging (T1-MRI), Evans Blue infusion and histology we measured intracranial tumor volumes in a rodent brain tumor model (RT2) at days 10, 16 and 18 after implantation of cells in the caudate putamen. There is a good correlation between tumor volumes comparing T1-MRI and Evans Blue (r2 = 0.99), T1-MRI and Histology (r2 = 0.98) and histology and Evans Blue (r2 = 0.93). Each of these methods is reliable in estimating tumor volumes in laboratory animals. There was significant uptake of gadolinium and Evans Blue in the tumor suggesting a wide disruption of the blood-brain barrier.

Animals↗
PubMed1999

An in vivo rat model for visualizing glioma tumor cell invasion using stable persistent expression of the green fluorescent protein.

In our studies examining mechanisms of brain tumor cell migration/invasion into host tissue, the RT2 rat glioma cell line was stably transfected utilizing a green fluorescent protein (GFP) DNA construct. Stable transfected RT2 cells demonstrate high GFP expression at initial passages, maintain expression over 30 passages and have similar in vitro and in vivo growth patterns relative to controls. In rat brain tissue, individual tumor cells can be detected without any post-treatment. Using flow cytometry and cell sorting, we are able to retrieve and culture GFP positive cells from tumor core as well as adjacent tissue and contralateral hemisphere of tumor-bearing animals.

Animals↗
PubMed1999

Measurement of the force required to move a neurosurgical probe through in vivo human brain tissue.

The advent of high-precision magnetic and robotic computer-controlled neurosurgery systems makes it necessary to determine the range of forces that will be encountered by the probes of such devices as they are guided through the brain tissues to intraparenchymal targets. We have measured the penetration forces on 2.5-mm spheres and the drag forces on 3.0-mm ventricular shunt catheters advanced 2.0-3.5 cm deep into in vivo human brain tissues (in patients about to have those tissues resected during epilepsy surgery) at rates of approximately 0.33 mm s-1. Penetration forces of (8 +/- 2) grams were found for the spherical probe once it passed 0.5 cm below the cortical surface, and frictional drags of (2.8 +/- 0.3) grams cm-1 were exerted on the catheters. The variable nature of these forces is discussed and the results are compared with earlier studies on experimental animal tissues and brain phantom gelatins. The implications of these results for magnetic and robotic surgery systems are considered.

Biomechanical Phenomena↗
PubMed1999

Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction.

OBJECT: The goal of this study was to determine whether adenoviral vector-mediated expression of human wildtype p53 can enhance the radiosensitivity of malignant glioma cells that express native wild-type p53. The p53 gene is thought to function abnormally in the majority of malignant gliomas, although it has been demonstrated to be mutated in only approximately 30%. This has led to studies in which adenoviral transduction with wild-type human p53 has been investigated in an attempt to slow tumor cell growth. Recent studies suggest that reconstitution of wild-type p53 can render cells more susceptible to radiation-mediated death, primarily by p53-mediated apoptosis. METHODS: Rat RT2 glioma cells were analyzed for native p53 status by reverse transcriptase-polymerase chain reaction and sequence analysis and for p53 expression by Western blot analysis. Clonogenic survival and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were used to characterize RT2 cell radiosensitivity and apoptosis, respectively, with and without prior transduction with p53-containing and control adenoviral vectors. Animal survival length was monitored after intracerebral implantation with transduced and nontransduced RT2 cells, with and without cranial radiation. The RT2 cells were demonstrated to express native rat wild-type p53 and to markedly overexpress human p53 following adenoviral p53 transduction. The combination of p53 transduction followed by radiation resulted in marked decreases in RT2 cell survival and increases in apoptosis at radiation doses from 2 to 6 Gy. Animals receiving cranial radiation after intracerebral implantation with RT2 cells previously transduced with p53 survived significantly longer than control animals (p<0.01). CONCLUSIONS: The ability to enhance the radiosensitivity of malignant glioma cells that express wild-type p53 by using adenoviral transduction to induce overexpression of p53 offers hope for this approach as a therapeutic strategy, not only in human gliomas that express mutant p53, but also in those that express wild-type p53.

Adenoviridae↗
PubMed1998

Distribution of macromolecular dyes in brain using positive pressure infusion: a model for direct controlled delivery of therapeutic agents.

BACKGROUND: Direct infusion of therapeutic agents into the brain is a novel technique that has the potential for bypassing the blood-brain barrier and delivering high concentrations of therapeutic agents into the brain parenchyma. We have developed a model to characterize the distribution of Evans Blue (MW 960) and Blue Dextran (MW 2 x 10(6)) in rat brain using a positive pressure infusion system. METHODS: Evans Blue and Blue Dextran were infused in volumes of 20, 40, 60, 100, 140, and 180 microL into the caudate putamen of female Fischer rats over a period of 2 h with rates of infusion varying between 0.167 microL and 1.5 microL/min. During the infusions, the pressure generated in the infusion system and intracranial pressure were measured using a fiberoptic pressure monitoring system. After infusions, the volumes of distribution of the dye molecules were measured from 3-mm thick sections using video microscopy and computer image analysis. Histologic changes during the infusion were studied using snap freezing and hematoxylin/eosin staining of cryosections. RESULTS: Volumes of distribution for Evans Blue were greater than those for Blue Dextran. There was extensive spread of each dye in the ipsilateral hemisphere and also across the corpus callosum to the opposite hemisphere. Infusion/interstitial pressures peaked during the first 5 min of the infusion period, after which pressures dropped to a plateau value that remained relatively constant during the remainder of the infusion. Histologic findings suggest that this phenomenon is an important transition process that is likely to play a role in the pattern of distribution of macromolecules infused by this technique. No marked changes in intracranial pressure were noted during the infusion procedure. CONCLUSIONS: Direct positive pressure infusion into the brain has great potential in the treatment of brain tumors and other central nervous system disorders using both high and low molecular weight compounds (immunotoxins, protein conjugates, pharmacologic agents, oligonucleotides, and viral vectors).

Animals↗
PubMed1998

An illuminating retractor for intracranial microneurosurgery.

During certain microneurosurgical procedures, the illumination provided by current coaxial microscope light sources is suboptimal. One potential solution is the surgical light blade (SLB), a malleable retractor incorporating a flat fiberoptic bundle along its surface. The SLB provides intense illumination within the surgical field without decreasing the amount of limited operating space. A prototype of the SLB was tested in six patients. Results suggest that with further development the SLB could become useful for intracranial microneurosurgery.

Brain Diseases↗
PubMed1998

Measurement of friction on straight catheters in in vitro brain and phantom material.

As part of our studies on the magnetic stereotaxis system (MSS), a means of delivering therapies to the bulk brain, we have measured the frictional forces on a thin, straight tube used to simulate a catheter. Experiments were done with a spring-loaded, stainless steel tube of 1.9-mm diameter which was passed through 5.5 cm of gelatin phantom or, alternatively, through in vitro calf brain. The dynamic response of the tube to sudden displacement of the outer end of the spring yields estimates of the tube's friction per unit length. Twenty-three runs in the two media were analyzed for the static and dynamic frictional forces exhibited. In these series the static frictional forces were found to be (0.0132 +/- 0.0012) N cm-1 [(1.32 +/- 0.12) g cm-1] of length in the gelatin phantom and (0.0079 +/- 0.0008) N cm-1 [(0.79 +/- 0.08) g cm-1] of length in brain. The kinetic friction coefficient, b, was found to be (8.4 +/- 2.1) N s m-1/cm length of catheter in brain and (16.3 +/- 7.6) N s m-1/cm length of catheter in the phantom material. Based on these figures, the MSS will be capable of moving straight catheters of similar friction that are 20-cm long at rates of displacement of 0.02 to 0.05 cm s-1 in the white and grey matter of the brain. Future studies will evaluate the forces arising from curved paths. Unanswered questions remain as to the mechanical difference between in vivo and in vitro brain, between animal and human brain, and the involvement of sulci in practical paths of motion.

Biomechanical Phenomena↗
PubMed1998

Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion.

OBJECT: High-flow microinfusion is a novel technique for delivery of compounds directly into brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into brain parenchyma represents an additional potential application of this technique not previously described. In this report the authors sought to examine the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) for this reason. METHODS: An 18-mer 35S-PS-ODN (Mr approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and was analyzed to determine the radioactivity and stability of the 35S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 +/- 210.5 nCi/g. This represents a tissue concentration of 19.2 +/- 0.84 microM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The 35S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 1% (50 +/- 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, but stabilized at a lower CSF content of 0.2% (1 +/- 0.1 nCi) thereafter. The volume of distribution was 105 +/- 7.9 mm3 at 1 hour, representing a volume of distribution/volume of infusion ratio of 5.2. The volume of distribution increased to 443 +/- 62.3 mm3 at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 microM to 3.2 microM. Undegraded 18-mer was observed throughout the 48-hour period by means of 20% polyacrylamide/7 M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity and minimal structural changes in tissue were observed on histological investigation. CONCLUSIONS: The authors found that PS-ODNs can be safely delivered in high concentrations to wide areas of rat brain by using high-flow microinfusion and are stable even after 48 hours in situ.

Animals↗
PubMed1997

Distribution and stability of antisense phosphorothioate oligonucleotides in rodent brain following direct intraparenchymal controlled-rate infusion.

High-flow microinfusion is a novel technique for delivery of compounds directly into the brain parenchyma, bypassing the blood-brain barrier. The feasibility of this technique has been demonstrated with low-molecular-weight compounds, macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into the brain parenchyma represents an additional potential application of this technique not previously described. In this report, the authors examined the distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN) infused for this reason. An 18-mer (35)S-PS-ODN (molecular weight approximately 6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1, 6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid (CSF) was also aspirated from the cisterna magna and analyzed for radioactivity and stability of the (35)S-PS-ODN. At 1 hour, the infused ODN was uniformly distributed in brain tissue, with a maximum average concentration of 4806.5 +/- 210.5 nCi/g. This represents a tissue concentration of 19.2 +/- 0.84 microM. Extensive spread into surrounding parenchyma was observed over the ensuing 47 hours. The (35)S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour infusion, containing 10% (50 +/- 20 nCi) of the infused radioactivity. Activity then decayed exponentially over 11 hours, stabilizing at a lower CSF content of 0.2% (1 +/- 0.1 nCi). The volume of distribution (V(d)) was 105 +/- 7.9 mm3 at 1 hour, representing a ratio of V(d)/V(i) (volume of infusion) of 5.2. The V(d) increased to 443.4 +/- 62.3 mm(3) at the end of 48 hours, whereas the average minimum tissue concentration decreased from 15.2 to 3.2 microM. Undegraded 18-mer was seen throughout the 48-hour period using 20% polyacrylamide/7M urea gel electrophoresis. The animals tolerated the infusion without evidence of toxicity, and minimal structural changes in tissue were observed on histological examination. Thus, PS-ODN can be safely delivered in high concentrations to wide areas of the rat brain by using high-flow microinfusion, and the concentrations remain stable even after 48 hours in situ.

Journal Article↗
PubMed1997

Antiproliferative effect of c-myc antisense phosphorothioate oligodeoxynucleotides in malignant glioma cells.

OBJECTIVE: To improve the prognosis for primary malignant tumors of the central nervous system, new therapeutic strategies are needed. Antisense oligodeoxynucleotides (ODNs) offer the potential to block the expression of specific genes within cells. The proto-oncogene c-myc has long been implicated in the control of normal cell growth and its deregulation in the development of neoplasia. We therefore reasoned that a strategy using ODNs complementary to c-myc messenger ribonucleic acid would be a potent inhibitor of glioma cell proliferation. METHODS: A variety of antisense, sense, and scrambled (15-mer) phosphorothioate ODNs targeted to rat and human c-myc messenger ribonucleic acid were synthesized and added to the media of cultured RT-2 cells (a rat glioblastoma cell line). Cell growth was assessed by 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide dye assay 1 to 5 days after adding the ODNs. c-Myc protein expression was analyzed by Western blot analysis. The stability of the ODNs was confirmed by gel electrophoresis. RESULTS: Compared with cultures containing standard media, two of three antisense ODNs significantly inhibited the growth of glioma cells, whereas sense and scrambled sequence ODNs did not significantly affect cell growth at the concentrations tested. A human c-myc antisense sequence, which differed from the rat sequence by one base substitution, also had an inhibitory effect on RT-2 cells. Western blot analysis demonstrated that expression of immunoreactive c-Myc protein was also greatly reduced in the rat antisense ODN-treated cells (and not in sense-, scrambled-, or control-treated cells). The degree of reduction of c-Myc protein expression correlated well with the decrease in cell growth observed with several antisense ODNs. Phosphorothioate ODNs were stable in cell culture media for at least 5 days. CONCLUSION: These results suggest that c-Myc plays a critical role in glioma cell proliferation and demonstrate that antisense ODNs can suppress proto-oncogene expression and inhibit the proliferation of glioma cells. Our results indicate that the antiproliferative activity of these ODNs was mediated predominantly through sequence-specific antisense mechanisms, but that sequence-specific nonantisense effects may also contribute to the strongest effects demonstrated. These findings support a potential role for antisense strategies designed to inhibit c-myc expression in the treatment of malignant gliomas.

Animals↗
PubMed1997

Utilization of type I collagen gel, demineralized bone matrix, and bone morphogenetic protein-2 to enhance autologous bone lumbar spinal fusion.

Autologous bone grafts are currently considered "gold standard" material for achieving long-term spinal arthrodesis. The present study was performed to determine whether demineralized bone matrix (DBM), type I collagen gels, or bone morphogenetic protein-2 (BMP-2) can improve autologous bone spinal fusions. Using a unilateral decompression-contralateral fusion technique in dogs, each of these materials was added to an autologous bone graft. Volumetric analysis, histological analysis, and biomechanical testing were performed to assess the effectiveness of each material. The DBM had an inhibitory effect on solid bone fusion of the spine, whereas the type I collagen gels improved the bony interface between the graft and the host spine. The BMP-2 strongly enhanced the amount of bone deposition at the fusion site and increased the number of intervertebral levels that were solidly fused. This study strongly supports the use of BMP-2 as an additive to autologous bone grafts in spine stabilization.

Animals↗
PubMed1996

Magnetic neurosurgery.

Because of the complex shape of many brain structures, the ideal brain probe would be highly flexible and give the neurosurgeon the ability to independently and precisely control movement of the probe tip. A magnetic surgery system has been developed that implements this concept. Flexible brain probes with small permanent magnetic tips are placed on the brain surface through a small burr hole and then magnetically manipulated within the brain. Drive forces are produced by an array of six superconducting magnets suspended within a cryostatic helmet. They produce a maximum force of 3 times the threshold needed to move the probe through the parenchymal tissues at its normal speed of 1 mm/s. Computer-controlled magnetic impulses precisely direct the probe movement in any direction desired with movement accuracy of 0.47 mm in phantom gels. Probe position is monitored 3 times per second with orthogonally oriented microchannel plate X-ray systems, X-ray dose from a 3-hour simulated procedure is comparable to that of a chest X-ray. In vivo and in vitro feasibility studies have been carried out in dog and pig brains. Preclinical trials are planned for clinical applications including implantation of flexible brachytherapy threads.

Equipment Design↗