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Biomedical subjects

J Glen

Publications and source records attributed to J Glen.

18 recordsLinked to original sources
PubMed2000

Adenoviral vector-mediated gene transfer: timing of wild-type p53 gene expression in vivo and effect of tumor transduction on survival in a rat glioma brachytherapy model.

OBJECTIVE: This study sought to investigate modification of the radiation response in a rat 9L brain tumor model in vivo by the wild-type p53 gene (wtp53). Determination of the timing and dose of radiation therapy required the assessment of the duration of the effect of wtp53 expression on 9L tumors after in vivo transfection. METHODS: Anesthetized male F-344 rats each were stereotactically inoculated with 4 x 10(4) 9L gliosarcoma cells through a skull screw into the cerebrum in the right frontal region. Twelve-day-old tumors were inoculated through the screw with recombinant adenoviral vectors under isoflurane anaesthesia: control rats with Ad5/RSV/GL2 (carrying the luciferase gene), and study rats with Ad5CMV-p53 (carrying the wtp53 gene). Brain tumors removed at specific times after transfection were measured, homogenized, and lysed and wtp53 expression determined by Western blot analysis. Four groups of nine rats were, subsequently, implanted with iodine-125 seeds 15 days post-tumor inoculation to give a minimum tumor dose of 40 or 60 Gy. RESULTS: We demonstrated transfer of wtp53 into rat 9L tumors in vivo using the Ad5CMV-p53 vector. The expression of wtp53 was demonstrated to be maximum between days 1 and 3 post-vector inoculation. Tumors expressing wtp53 were smaller than controls transfected with Ad5/RSV/GL2 but this difference was not statistically significant. Radiation made a significant difference to the survival of tumor-bearing rats. Moreover, wtp53 expression conferred a significant additional survival advantage. CONCLUSION: The expression of wtp53 significantly improves the survival of irradiated tumor-bearing rats in our model.

Adenoviridae↗
PubMed2000

Quality of life in patients with glioblastoma multiforme participating in a randomized study of brachytherapy as a boost treatment.

OBJECT: Until recently the assessment of outcome in patients treated for glioma has emphasized length of survival with the evaluation of quality of life (QOL) limited to unidimensional, mostly physical, measures. The authors report the multidimensional assessment of QOL as part of a randomized clinical trial of brachytherapy as a boost in the initial treatment of patients with glioblastoma multiforme. METHODS: A questionnaire previously developed by the senior authors and psychometrically validated was completed by patients on randomized entry into the study and at follow-up review every 3 months thereafter. The questionnaire was presented in a linear-analog self-assessment format. Karnofsky Performance Scale (KPS) scores were also recorded on each occasion. No differences were found between patients in either arm of the study (conventional radiation therapy consisting of 50 Gy in 25 fractions or conventional radiation plus a brachytherapy boost of a minimum peripheral tumor dose of 60 Gy) in KPS and QOL scores during the 1st year of follow-up review. However, there was a statistically significant deterioration in patients' overall KPS scores during the 1st year of follow up compared with baseline scores. Of QOL items evaluated, statistically significant deteriorations were found in self care, speech, and concentration, and on subscale analyses, cognitive functioning and physical experience (symptoms) deteriorated significantly during the 1st year of follow up, compared with baseline values. The correlation between QOL and KPS scores was low. CONCLUSIONS: Future studies in patients harboring malignant gliomas must incorporate measures assessing QOL because traditional measures focusing on physical or neurological functioning give an incomplete assessment of the patient's experience.

Adolescent↗
PubMed1998

Randomized study of brachytherapy in the initial management of patients with malignant astrocytoma.

PURPOSE: A randomized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas. METHODS AND MATERIALS: Inclusion criteria included the following: biopsy-proven supratentorial malignant astrocytoma of brain < or =6 cm in size, not crossing midline or involving corpus callosum, age 18-70, Karnofsky Performance Status (KPS) > or =70. Patients were randomized to external radiation therapy only delivering 50 Gray (Gy) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy. Patients were stratified to age < or =50 or >50, and KPS > or =90 or < or =80. RESULTS: There were 140 patients randomized between 1986 and 1996, 71 to the implant arm and 69 to external irradiation only. Pathologically 125 patients had necrosis noted in their tumor specimen. Factors associated with improved survival in univariate analysis were age < or =50, KPS > or =90, chemotherapy at recurrence, and reoperation at the original tumor site. The Cox proportional hazards model revealed the following significant factors: treatment at recurrence (chemotherapy or reoperation) with a relative risk (RR) of 0.6 (p = 0.004) and KPS > or =90 with a RR 0.6 (p = 0.007). Randomization to the implant arm was associated with a RR of 0.7 (p = 0.07). Median survival for patients randomized to brachytherapy or not were 13.8 vs. 13.2 months, respectively, p = 0.49. CONCLUSIONS: We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma.

Adult↗
PubMed1997

Effect of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model: implications for brain tumor therapy.

OBJECTIVE: This study sought to investigate the effects of implant dose/volume and surgical resection on survival in a rat glioma brachytherapy model. Two doses were investigated to determine a suitable therapeutic range. METHODS: We performed two experiments. Three treatment groups and one control group of male F-344 rats bearing 9L brain tumors 12 days after tumor inoculation were used in the first experiment. Day 12 tumors were an average of 4 to 6 mm in diameter. Animals treated with brachytherapy received a tumor dose of 80 Gy delivered to a 5.5-mm-radius volume. Total macroscopic tumor removal was achieved by microsurgical techniques. A subsequent experiment compared the survival of tumor-burdened rats treated with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume with a control group. RESULTS: Surgery alone produced an increased life span of 28.6% over control animals treated with sham surgery and dummy seed implants, a statistically significant increase in survival (P = 0.0023, log-rank test). Brachytherapy alone produced the most significant increase in survival over control animals (P = 0.0001, log-rank test; median survival not attained with an implant dose of 80 Gy delivered to a 5.5-mm-radius volume; and P = 0.0001, increased life span 121% with an implant dose of 60 Gy delivered to a 5.5-mm-radius volume). This was not improved by the addition of surgical tumor removal. CONCLUSION: We have demonstrated a relationship between implant dose/volume and survival of tumor-burdened rats in this model that is not improved by the addition of tumor removal. Implications for brain tumor brachytherapy are discussed.

Animals↗
PubMed1996

Tirilazad does not protect rat brain from brachytherapy-induced injury.

BACKGROUND: Acute and chronic brain injury are common sequelae of high-dose focused radiation, as in radiosurgery and brachytherapy. Development of protectors of radiation injury, which would work in brain but not in tumor, would help enhance the therapeutic ratio of focused-radiation therapy. METHODS: Radiation protection by a clinically available 21-aminosteroid, Tirilazad, was studied in a rat brain brachytherapy model, both in tumor and non-tumor bearing animals. For the tumor model, 9L Glioma/SF line cells were implanted stereotactically into the right frontal lobe of F-344 rats and grew to a sphere of 5.0-mm diameter after 12 days. Animals received a standard brachytherapy dose of 80 Gy to a 5.5-mm radius volume administered by a high-activity removable iodine-125 seed. Radiation damage was evaluated 24 hours after removal of the seeds in all animals and again at 3 months in non-tumor-bearing animals, by T1-weighted gadolinium-enhanced and T2-weighted magnetic resonance imaging (MRI) on a 1.5-T unit. Treated animals received Tirilazad 5 mg/kg intravenously 15 minutes prior to implant, 1 hour after implant, every 6 hours for the duration of the implant, and for 24 hours after removal of the seed. Control animals were administered vehicle only. RESULTS: In both non-tumor-bearing and tumor-bearing rats, no difference in the volume of lesions on enhanced T1 or T2 MRI was seen between the Tirilazad-treated and control groups. In the non-tumor-bearing rats, volume of both T1 enhanced and T2 MRI lesions was significantly reduced at 3 months compared to the values at 24 hours. CONCLUSIONS: In the present model, Tirilazad failed to reduce the volume of radiation brain injury from brachytherapy as seen on MRI, studied acutely in tumor-bearing and non-tumor-bearing animals and also at 3 months in non-tumor-bearing rats.

Animals↗
PubMed1995

Stereotactic high-activity brachytherapy for malignant intra-axial brain tumors. Status report as of March, 1995.

Over the last several decades in Europe and 15 years in North America, numerous centers have used stereotactic high-activity brachytherapy for patients with malignant brain tumors. A number of nonrandomized series have contributed information regarding the efficacy compared to historical controls for patients with de novo and recurrent malignant gliomas and metastases. Two randomized studies for patients with de novo malignant astrocytoma and glioblastoma are nearing completion. Based on the author's personal experience with 115 patients and the reported literature, we conclude that brachytherapy is appropriate for a minority of patients with malignant brain tumors, that reoperation is frequently required, and complications of therapy can be significant. However, a proportion of highly selected patients benefit significantly from this therapy.

Astrocytoma↗
PubMed1994

Brachytherapy for recurrent malignant astrocytoma.

PURPOSE: To assess the efficacy of interstitial brachytherapy in the treatment of patients with recurrent malignant astrocytoma. METHODS AND MATERIALS: Forty-six patients with recurrent malignant astrocytoma were treated with stereotactic high-activity temporary iodine-125 implants between September, 1986 and October, 1992. All patients had been initially treated for malignant astrocytoma (44) or low-grade astrocytoma (2) with surgery and external fractionated radiation. The median time between initial diagnosis and recurrence treated with brachytherapy was 12.5 months. Twenty-five patients received chemotherapy prior to brachytherapy. RESULTS: All but four patients have died; median survival time following brachytherapy is 46 weeks. Twelve patients underwent reoperation for radiation necrosis at a median interval of 6.5 months after treatment (26%). Five patients incurred complications directly due to brachytherapy (11%). Forty-four patients are evaluable regarding pattern of failure following brachytherapy. Six of these 44 patients (13.6%) recurred at a distance from the treatment volume (4 in brain and 2 in spinal subarachnoid space). CONCLUSION: Brachytherapy confers modest but meaningful prolongation of survival in selected patients with recurrent malignant astrocytoma, but complications are significant, reoperation frequently required, and recurrence outside the treatment volume common.

Adolescent↗
PubMed1994

Did I do right?

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Ethics, Nursing↗
PubMed1992

Protection of iodine-125 brachytherapy brain injury in the rat with the 21-aminosteroid U-74389F.

Radiation protection was studied in a rat brachytherapy brain injury model. Radiation lesions were produced by stereotactic placement of high-activity iodine-125 seeds on the frontal lobe of F-344 rats. A minimum dose of 80 Gy was delivered to a 5.5-mm-radius volume. Radiation damage was evaluated 24 h after removal of the seeds by T1-weighted gadolinium-enhanced magnetic resonance imaging on a 1.5-T unit. Computerized three-dimensional reconstruction of the lesions seen on magnetic resonance imaging was performed to calculate the volume of radiation injury. Two experiments were performed with rats of different weights (mean, 300 g; mean, 180 g). All animals underwent surgical placement of an indwelling internal jugular catheter before brachytherapy. Treated animals received the 21-aminosteroid U-74389F 5 mg/kg intravenously every 6 hours during the implant and for 24 hours after the removal of the iodine-125 seed. Control animals were administered vehicle only. In both experiments, a statistically significant reduction in volume of radiation damage was observed in the U-74389F-treated group compared with the control group.

Animals↗
PubMed1990

Brain damage from 125I brachytherapy evaluated by MR imaging, a blood-brain barrier tracer, and light and electron microscopy in a rat model.

Changes in normal rat brain were studied acutely, and at 3, 6, 9, and 12 months following interstitial brachytherapy with high-activity 125I seeds. An 80-Gy radiation dose was administered to an area with a 5.5-mm radius. Effects were measured with magnetic resonance (MR) imaging (with and without gadolinium enhancement), leakage of horseradish peroxidase (HRP), electron microscopy, and light microscopy. Significant histological damage was seen at radiation doses above 295 Gy, and breakdown of the blood-brain barrier was observed only in tissue receiving a dose of 165 Gy or greater. Blood-brain barrier breakdown increased up to the 6-month time point, and thereafter appeared to stabilize or decrease. The area of blood-brain barrier disruption indicated by gadolinium-enhanced MR imaging was greater than that indicated by leakage of HRP.

Animals↗
PubMed1988

What's in a report?

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Continuity of Patient Care↗
PubMedDate not supplied

Young Investigator Award. Percutaneous facet joint fusion: preliminary experience.

PURPOSE: The synovium-lined apophysial joint is an important cause of back pain through facet arthrosis and nerve root pressure. The short-term results of two relatively noninvasive treatments--facet block and facet rhizotomy--have been better than their long-term results. The authors propose treatment with fusion of the posterior facet joints in the lumbar spine by means of a simple percutaneous procedure performed under local anesthetic with use of radiologic guidance. MATERIALS AND METHODS: In the first phase of this study the technical feasibility of the concept was established in human cadaver spine. In the second phase a canine model was tested in which bone grafts were surgically inserted into lumbar facet joints. Five male and two female mongrel dogs, weighing 18-25 kg (mean, 20.3 kg), were operated on. Each procedure was done in three steps: First, preoperative computed tomographic (CT) scans were obtained to measure facet depth. Second, surgery was performed under fluoroscopic guidance with use of a threaded guide wire, a small cannulated coaxial drilling system, and hydroxyapatite cancellous bone plugs. Third, early postoperative CT scans were obtained to verify bone plug location. CT was repeated at 4 and 6 months after surgery to check for fusion. The dogs were killed at 6 months, and histologic examination was performed. RESULTS: Successful insertion of the bone plug was achieved in 12 of the 14 facets (86%). One dog died as a complication of the procedure. Fusion occurred in five of the 12 surgically treated facets (42%). CONCLUSION: Drilling and surgical insertion of bone plugs into facet joints of dogs were feasible. The fusion results are promising and may improve with future modifications of the technique.

Anesthesia, Local↗
PubMedDate not supplied

The rhesus monkey as an animal model for training in interventional neuroradiology.

The angiographic anatomy of the external carotid artery system in the rhesus monkey is described. Similarities and differences between human and monkey anatomy are emphasized, as well as anatomic variations and potential collateral pathways. Superselective angiography and embolization in the external carotid artery system of the rhesus monkey proved to be technically feasible and potentially represents an excellent training model for surgical neuroangiographic techniques.

Animals↗
PubMedDate not supplied

Elective neurosurgical office consultations: how well are patients informed?

A prospective study was performed on elective neurosurgical office referrals to one neurosurgeon at the Toronto Hospital from September 1988 to May 1996. Patient level of information was tested using the chisquare test on the study population of 2,017 patients grouped according to the type of referring doctor and regional category of diagnosis. There was a statistically significant difference in the degree of knowledge of referred patients according to the type of referring doctor (p < 0.008). In addition there was statistical significance found in the difference in degree of knowledge among patients referred with the various regional categories of disease (p < 0.008). Patients referred by family physicians are not as informed as to the nature of their neurosurgical referral as those referred by neurologists and other specialists. Furthermore, patients with an intracranial diagnosis had a greater level of knowledge about their referral than those patients referred for spinal, peripheral nerve or other diagnoses.

Health Knowledge, Attitudes, Practice↗