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1.
Clin Transl Radiat Oncol ; 33: 1-6, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34977365

ABSTRACT

BACKGROUND AND PURPOSE: Transient tumor swelling is a well-known phenomenon following radiotherapy for vestibular schwannomas (VS). We analyzed the long-term volumetric changes of VS after LINAC radiosurgery, in order to determine a time interval during which a true tumor progression can be distinguished from a pseudoprogression. METHODS: Among 63 patients with VS treated by one fraction or fractionated radiotherapy, we selected 52 of them who had a minimal follow-up of 5 years. Maximal axial diameter and three-dimensional tumor volume were measured on each MRI scan. Volume changes were interpreted using different error margins ranging from 10 to 20%. Patients were categorized according to the tumor evolution pattern over time. RESULTS: Median follow-up was 83 months. One tumor (1.9%) remained stable and 26.9% had continuous shrinkage. Applying an error margin of 13%, a transient tumor enlargement was observed in 63.5% of patients, with a first peak at 6-12 months and a late peak at 3-4 years. A true progression was suspected in 4 (7.7%) patients, tumor regrowth starting after the 3rd or 4th year post-treatment. Only one patient required salvage radiotherapy. CONCLUSION: Transient swelling of VS following radiotherapy is generally an early phenomenon but may occur late. In the first 5 years, a true tumor progression cannot be differentiated from a pseudoprogression. A significant tumor expansion observed on 3 sequential MRI scans after the 3rd year may be suggestive of treatment failure. Long-term follow-up is therefore mandatory and no decision of salvage treatment should be made until the 6th year.

2.
Cancer Radiother ; 25(2): 141-146, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33422416

ABSTRACT

PURPOSE: The ultimate goal of stereotactic radiotherapy (SRT) of brain metastases (BM) is to avoid or postpone whole brain radiotherapy (WBRT). A nomogram based on multi-institutional data was developed by Gorovets, et al. to estimate the 6 and 12-months WBRT-free survival (WFS). The aim of the current retrospective study was to validate the nomogram in a cohort of postoperative BM patients treated with adjuvant SRT. MATERIAL AND METHODS: We reviewed the data of 68 patients treated between 2008-2017 with postoperative SRT for BM. The primary endpoint was the WFS. The receiver operating characteristic curve and area under the curve (AUC) were calculated for both 6- and 12-months time points. RESULTS: After a median follow-up of 64 months, the 1-year cumulative incidence of local and distant brain relapse rates were 15% [95% CI=8-26%] and 34% [95% CI=24-48%], respectively. At recurrence, repeated SRT or salvage WBRT were applied in 33% and 57% cases, respectively. The WFS rates at 6 and 12 months were 88% [95% CI=81-97%] and 67% [95% CI=56-81%], respectively. Using the Gorovets nomogram, the 6 months rates were overestimated while they were accurate at 12 months. AUC values were 0.47 and 0.62 for the 6- and 12-months respectively. Overall, Harrell's concordance index was 0.54. CONCLUSION: This nomogram-predicted well the 12 months WFS but its discriminative power was quite low. This underlines the limits of this kind of predictive tool and leads us to consider the use of big data analysis in the future.


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/secondary , Cranial Irradiation , Nomograms , Radiosurgery/methods , Salvage Therapy/methods , Adult , Aged , Aged, 80 and over , Area Under Curve , Brain Neoplasms/epidemiology , Brain Neoplasms/surgery , Confidence Intervals , Cranial Irradiation/statistics & numerical data , Female , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Postoperative Period , ROC Curve , Radiosurgery/statistics & numerical data , Retrospective Studies , Salvage Therapy/statistics & numerical data , Time Factors
3.
Cancer Radiother ; 24(4): 298-305, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32173270

ABSTRACT

PURPOSE: To retrospectively analyze the outcomes of stereotactic radiotherapy (SRT) targeted at surgical bed of brain metastases (BM) and identify patterns of local/distant brain relapses (LR/DBR). PATIENTS/METHODS: Seventy patients were treated with SRT between 2008-2017. Marginal dose prescription on the 70% isodose line depended on the maximal diameter of the target volume and range between 15-18Gy for single fraction radiosurgery and 23.1-26Gy in 3-5 fractions for fractionated SRT. RESULTS: At 12 months, the overall survival (OS) was 69% [CI 95%=59%-81%]. At 6 and 12 months, the cumulative incidence functions (CIF) of local relapse were 4% [1%-13%] and 15% [8%-26%], respectively. According to univariate analysis, factors associated with LR were an initial volume larger than 7cc (hazard ratio: 4.6 [1.0-20.8], P=0.046) and a positive resection margin [hazard ratio: 3.6 [1.1-12.0], P=0.037. DBR occurred in 54.3% of patients with a median time of 8 months. None of the variables tested (histology, location or number of lesions) were found correlated with the DBR. Leptomeningeal disease occurred in 12.9% of cases. Salvage whole brain radiotherapy (WBRT) was required in 45.7% of patients and delayed by a median time of 9.6 months. Symptomatic radionecrosis (RN) occurred in 7.1%. CONCLUSIONS: Adjuvant SRT was an effective and well-tolerated treatment to control the postoperative risk of recurrence of BM without compromising OS. Positive resection margins and large volumes were predictors factor of local relapse.


Subject(s)
Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Radiosurgery/methods , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Brain Neoplasms/secondary , Cranial Irradiation/statistics & numerical data , Female , Humans , Male , Margins of Excision , Meningeal Neoplasms/epidemiology , Middle Aged , Necrosis/epidemiology , Neoplasm Recurrence, Local , Progression-Free Survival , Radiation Injuries/epidemiology , Radiosurgery/mortality , Radiotherapy Dosage , Retrospective Studies , Salvage Therapy/statistics & numerical data , Treatment Outcome , Tumor Burden
4.
Neurophysiol Clin ; 38(4): 227-33, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18662619

ABSTRACT

OBJECTIVE: To assess and compare, clinically and electrophysiologically, the effects on muscle innervation and spasticity of selective anaesthetic nerve block and selective neurotomy of the motor-nerve branch to the soleus muscle in patients with spastic equinus foot. METHODS: Eleven hemiplegic patients were studied before and after anaesthetic tibial-nerve block, and at two months and one year after tibial nerve neurotomy. Triceps surae spasticity and strength, walking speed, gait kinematics of the ankle, maximal amplitude of the H reflex and of the M-response and the Hmax/Mmax ratio of the soleus muscle, and the mean motor unit action potential area and motor unit number estimation (MUNE) of the soleus muscle were calculated on the normal and spastic side. RESULTS: Spasticity and equinovarus improved in a similar fashion after tibial nerve block and neurotomy. The soleus Hmax/Mmax ratio decreased by 42% after tibial nerve block and 77% after neurotomy. The soleus MUNE decreased by 52% after tibial nerve block and by 86% after neurotomy. CONCLUSION: Diagnostic nerve block predicts the spasticity and gait improvement, which is expected after neurotomy. The clinical improvement was similar after block and neurotomy. Nerve block is associated with a 50% decrease in the soleus Hmax/Mmax ratio and soleus MUNE. The median 80% neurotomy is associated with an 80% decrease in the soleus Hmax/Mmax ratio and soleus MUNE.


Subject(s)
Foot Deformities, Acquired/physiopathology , H-Reflex/physiology , Motor Neurons/physiology , Muscle Fibers, Skeletal/physiology , Muscle Spasticity/physiopathology , Muscle, Skeletal/physiopathology , Nerve Block , Tibial Nerve , Action Potentials/physiology , Adult , Biomechanical Phenomena , Electrophysiology , Female , Gait , Hemiplegia/physiopathology , Humans , Male , Middle Aged , Muscle, Skeletal/innervation , Prospective Studies
5.
Neurochirurgie ; 53(5): 343-55, 2007 Nov.
Article in French | MEDLINE | ID: mdl-17881014

ABSTRACT

OBJECTIVE: Internet has become the first place where patients go to when seeking information about their disease. Little is known about the type and the quality of the medical information available on French-speaking websites, especially in the field of neuro-oncology. The purpose of this study was to evaluate the quality of these sites. MATERIALS AND METHODS: We entered six key words "glioblastome", "méningiome", "métastase cérébrale", "neurinome de l'acoustique", "adénome à prolactine" and "lymphome primitif cérébral" into 2 different search engines and, for each key word, the first fifty websites were reviewed using the tool "DISCERN", and with the help of two neuro-oncologists, we rated their content in terms of quality and comprehension. RESULTS: On 612 websites only 110 (18%) contained information that proved to be somewhat useful to patients. The average score for quality was 32, which is considered to be <>. According to our scoring system, 1.8% of websites were found to be "excellent", 11.8% "good", 24.5% "fairly good", 15.4% "average", 32.7% "poor" and 13.6% "very poor". Just over 50% of the websites were found to be clear. The study also showed that the order in which these websites were ranked in the search engine, their affiliation, their target or who financed them had little impact on quality. The websites were more likely to be of high quality if they were managed by doctors and had bibliographical references as well as a date indicating a recent website's update. DISCUSSION AND CONCLUSION: This study shows that the search for medical information on the Internet is time consuming and often disappointing: very few websites provide information that is both clear and exhaustive. However, we also found that very few websites contained information that was seriously inaccurate. Given the growing popularity of the Internet, patients could certainly benefit from a high quality French speaking website that would specialize in cerebral tumors, as well as from a neuro-oncological portal that would take them to selected websites as it would save time and would be a guarantee for quality.


Subject(s)
Information Dissemination , Internet , Nervous System Neoplasms , France , Information Storage and Retrieval , Internet/standards , Language , Neurosurgery , Patient Education as Topic
6.
Neurochirurgie ; 53(5): 383-6, 2007 Nov.
Article in French | MEDLINE | ID: mdl-17706729

ABSTRACT

Ventricular schwannomas are very uncommon. We report such a tumor in the right lateral ventricle of a 16-year-old young man. The various etiopathogenic hypotheses are discussed.


Subject(s)
Cerebral Ventricle Neoplasms/surgery , Neurilemmoma/surgery , Adolescent , Cerebral Ventricle Neoplasms/pathology , Epilepsies, Partial/etiology , Humans , Immunohistochemistry , Lateral Ventricles/pathology , Magnetic Resonance Imaging , Male , Neurilemmoma/pathology , Neurosurgical Procedures , Tomography, X-Ray Computed
8.
Eur J Pediatr Surg ; 12(4): 230-4, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12368998

ABSTRACT

PURPOSE: To review and discuss the complications of minimally invasive pectus excavatum repair. METHODS: 329 patients underwent minimally invasive pectus repair between January 1987 and August 2000, including 14 patients who recurred after previous Ravitch repairs, 10 failed Nuss repairs (eight done elsewhere) and two failed Leonard repairs. All patients received antibiotics and vigorous incentive spirometry to prevent atelectasis, pneumonia and bar infection. Epidural anesthesia was used for postoperative analgesia to keep patients comfortable and stable postoperatively and to prevent bar displacement. Thoracoscopy was used during bar insertion to minimize the risk of mediastinal injury and to select the best position for the bar. A new introducer was developed to elevate the sternum before bar insertion. A stabilizing bar was created to minimize bar displacement. The duration of sternal bracing has been increased from two years to three or four years in selected patients. COMPLICATIONS: There were no deaths, no cardiac perforations and no cases of thoracic chondrodystrophy. Pneumothorax with spontaneous resolution occurred in 52 % of the patients, with 1.2 % requiring simple aspiration and 1.5 % requiring chest tube drainage. This complication has essentially been eliminated by using a "water seal system". Pericarditis occurred in 2.4 % with good response to Indomethacin in six out of eight patients and two patients also required pericardial fluid aspiration. Pneumonia occurred in 0.9 %. Wound infection occurred in 2.6 % resulting in bar infection in three out of the seven patients. Long-term antibiotics were successful in curing the infection in one patient, whereas the other two required bar removal at 12 and 18 months, respectively. Bar displacement occurred in 8.8 % of patients. However, the introduction of stabilizers decreased the incidence from 15.7 % before the use of stabilizers to 5.4 % with stabilizers. Wiring the bar and stabilizer together has decreased the incidence even further. RESULTS: Long-term outcome after bar removal showed an excellent result in 71 %, good result in 21 % and recurrence in 7.8 %. CONCLUSION: The minimally invasive technique has a low complication rate with excellent long-term results.


Subject(s)
Funnel Chest/surgery , Postoperative Complications/etiology , Thoracoscopy/methods , Adolescent , Adult , Child , Child, Preschool , Humans , Infant , Pericarditis/etiology , Pneumothorax/etiology , Retrospective Studies , Treatment Outcome
9.
Acta Neurochir (Wien) ; 143(7): 733-6, 2001.
Article in English | MEDLINE | ID: mdl-11534696

ABSTRACT

The case of a 20-year-old man presenting with a rapidly expanding pituitary somatotrophic adenoma with a tumour volume doubling time of 426 days is reported. Preoperative octreotide therapy induced a 45% tumour shrinkage and proliferating cells were absent at the time of tumoural resection. The correlation between clinical and proliferation markers data in this single case report affords an opportunity to discuss the antitumoral effect of octreotide on somatotrophic adenomas which may result from a suppression of cell proliferation.


Subject(s)
Adenoma/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Growth Hormone/antagonists & inhibitors , Neoplasm Recurrence, Local/drug therapy , Octreotide/therapeutic use , Pituitary Neoplasms/drug therapy , Adenoma/diagnosis , Adenoma/pathology , Adult , Humans , Male , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/pathology , Pituitary Neoplasms/surgery , Treatment Outcome
10.
Acta Orthop Belg ; 67(1): 1-5, 2001 Feb.
Article in French | MEDLINE | ID: mdl-11284266

ABSTRACT

Spasticity is usually treated by rehabilitation, orthosis, chemical denervations, orthopaedic surgery and neurosurgery. Selective fascicular neurotomy is a neurosurgical procedure consisting in partial section of selected motor nerves innervating spastic muscles. Neurotomy is indicated in cases of localised disabling spasticity without musculotendinous shortening, resistant to chemical denervation and for which a motor nerve block with anaesthetic has given a good functional result. Neurotomy includes division of the afferent Ia and Ib fibers, unable to recover, leading to permanent disappearance of the spasticity. Neurotomy also includes section of the motor efferent fibers with transient paresis as a result. In adults, neurotomy provides functional improvement in 81 to 97% of cases. In case of posterior tibial neurotomy, improved walking stability and a decrease in foot equinus and knee recurvatum is observed. In children, the risk of deformity recurrence seems higher because of motor axonal reinnervation: indications must therefore be carefully considered and rehabilitation provided after surgery.


Subject(s)
Cerebral Palsy/complications , Equinus Deformity/etiology , Equinus Deformity/surgery , Muscle Denervation/methods , Muscle Spasticity/etiology , Muscle Spasticity/surgery , Afferent Pathways/surgery , Disabled Persons , Efferent Pathways/surgery , Humans , Nerve Block/methods , Preoperative Care , Recurrence , Treatment Outcome
11.
Am J Surg Pathol ; 25(1): 127-30, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11145247

ABSTRACT

Intracranial meningiomas are generally slow-growing neoplasms. Symptoms depend on their critical intracranial location. The authors describe a case of rapidly enlarging meningioma that became symptomatic as a result of invasion by leukemic cells at the time of a blastic crisis in the context of chronic myeloid leukemia. Infiltration of an intracranial meningioma by cells from extracranial malignant neoplasms is a rare event. Even though central nervous system (CNS) or meningeal involvement is common in some hematologic malignancies, this is, to the best of our knowledge, the first report of invasion of an intracranial meningioma by leukemic cells.


Subject(s)
Leukemic Infiltration/pathology , Meningeal Neoplasms/pathology , Meningioma/pathology , Aged , Breast Neoplasms , Fatal Outcome , Female , Humans , Neoplasms, Multiple Primary/pathology
12.
Neurosurg Focus ; 10(4): E8, 2001 Apr 15.
Article in English | MEDLINE | ID: mdl-16732635

ABSTRACT

OBJECT: In cases of spondylosis or spine trauma, cervical interbody grafts are sometimes required after anterior discectomy. To avoid morbidity related to the harvesting of iliac crest bone, numerous materials have been developed such as allografts, methylmethacrylate, biocompatible osteoconductive polymer, and coralline grafts or cages. Some of these materials, however, are inefficient for fusion or are associated with specific complications. Conversely, hydroxyapatite (HA) grafts have numerous advantages. For example, their mechanical properties provide adequate load resistance and their porosity allows infiltration by newly formed bone, leading to complete fusion. The authors studied the results of using HA grafts combined with plating in patients who underwent anterior cervical discectomy. METHODS: Fifty-four patients underwent 68 cervical interbody fusion procedures in which an HA graft and plating were used. Indications for surgery were radiculopathy (caused by soft-disc herniation or spondylosis) in 46 cases, spondylotic myelopathy in two cases, and spinal trauma in six cases. Postoperatively the patients were followed for a mean of 24.6 months. Patients underwent radiography to evaluate fusion, intervertebral disc height, and the degree of lordosis. Clinically, excellent or good results (based on the Odon classification) were demonstrated in 91% of patients who presented with radiculopathy. Complete interbody fusion was achieved in 99% of all cases. Preoperative kyphotic deformities were corrected in all cases after surgery. Intervertebral disc height was maintained throughout follow up. Surgery-related morbidity was low; only one patient suffered from a permanent dysphagia. Graft deterioration was observed in 13 cases and two graft fractures occurred but without adversely affecting fusion. There were no cases of graft extrusion. CONCLUSIONS: Hydroxyapatite grafts are very efficient in achieving cervical fusion, maintaining intervertebral disc height, and restoring lordosis. When combined with the placement of a cervical plate, immediate stability is achieved and graft displacement is prevented.


Subject(s)
Biocompatible Materials/therapeutic use , Bone Plates , Cervical Vertebrae/surgery , Durapatite/therapeutic use , Prostheses and Implants , Spinal Fusion , Adult , Aged , Biocompatible Materials/adverse effects , Bone Screws , Cervical Vertebrae/diagnostic imaging , Diskectomy , Durapatite/adverse effects , Equipment Failure , Female , Humans , Kyphosis/surgery , Male , Middle Aged , Radiography , Spinal Diseases/surgery , Spinal Injuries/surgery , Treatment Outcome
13.
Spinal Cord ; 37(4): 301-4, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10338354

ABSTRACT

Cervical spinal fracture and pseudarthrosis are previously described causes of spinal cord injury (SCI) in patients with spondylarthropathy. SAPHO (Synovitis Acne Pustulosis Hyperostosis Osteitis) syndrome is a recently recognized rheumatic condition characterized by hyperostosis and arthro-osteitis of the upper anterior chest wall, spinal involvement similar to spondylarthropathies and skin manifestations including palmoplantar pustulosis and pustular psoriasis. We report the first case of SAPHO syndrome disclosed by SCI related to cervical spine ankylosis.


Subject(s)
Acquired Hyperostosis Syndrome/complications , Ankylosis/complications , Spinal Cord Injuries/etiology , Acquired Hyperostosis Syndrome/diagnostic imaging , Acquired Hyperostosis Syndrome/pathology , Aged , Ankylosis/diagnostic imaging , Ankylosis/pathology , Humans , Magnetic Resonance Imaging , Male , Spinal Cord Injuries/diagnostic imaging , Spinal Cord Injuries/pathology , Tomography, X-Ray Computed
14.
J Nurs Adm ; 29(4): 25-32, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10200783

ABSTRACT

Healthcare organizations are challenged to provide an environment that enhances professional growth. Miami Valley Hospital responded by examining its evaluation system for clinical nurses and designing a developmental evaluation process. The result is an objective position description outlining global responsibilities of a nurse and a comprehensive, unit-specific assessment of performance. As nurses are guided and nurtured in their development, the opportunities for them to excel are unlimited.


Subject(s)
Employee Performance Appraisal/organization & administration , Nursing Staff, Hospital/standards , Staff Development/methods , Consultants , Employee Performance Appraisal/standards , Hospital Units/organization & administration , Humans , Job Description , Nursing Staff, Hospital/organization & administration , Ohio , Organizational Innovation
15.
J Nurs Adm ; 28(10): 33-9, 1998 Oct.
Article in English | MEDLINE | ID: mdl-9787678

ABSTRACT

Clinical ladders help maintain expert, motivated, and effective nurses in direct patient care roles. While many institutions were phasing out clinical ladders for registered nurses, Miami Valley Hospital was proactively evaluating the original version. The authors describe their clinical advancement program, based on Benner's model, with program evaluation results. The program participation rate has increased overall. Participants perceive their work and environment more positively than nonparticipants.


Subject(s)
Career Mobility , Nursing Staff, Hospital/organization & administration , Program Development , Employee Incentive Plans , Evaluation Studies as Topic , Humans , Models, Nursing , Nursing Staff, Hospital/standards , Ohio , Organizational Innovation , Organizational Objectives , Power, Psychological , Quality of Health Care , Salaries and Fringe Benefits
16.
J Neurosurg ; 88(4): 773-6, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9525728

ABSTRACT

The authors describe an unusual case of a complex traumatic fracture-dissociation injury of the craniovertebral junction, which the patient survived with no neurological damage. This case featured the rare combination of an avulsion of both the right occipital condyle and clivus and a fracture of the left lateral mass of the atlas. Because of the craniocervical ligament injury and the slight anterior occipitoatlantal dislocation, the lesion was considered to be unstable and was treated successfully with a cervical collar. The authors emphasize that thin-slice computerized tomography scanning with multiplanar reconstructions is essential to visualize these fractures, whereas magnetic resonance imaging is useful to assess soft tissues.


Subject(s)
Atlanto-Occipital Joint/injuries , Fractures, Bone/diagnosis , Fractures, Bone/physiopathology , Nervous System/physiopathology , Adult , Atlanto-Occipital Joint/diagnostic imaging , Atlanto-Occipital Joint/pathology , Fractures, Bone/therapy , Humans , Magnetic Resonance Imaging , Male , Orthotic Devices , Tomography, X-Ray Computed
17.
Gene Ther ; 3(4): 315-22, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8732163

ABSTRACT

The herpes simplex virus thymidine kinase gene was transferred into C6 glioma cells by infection with a recombinant adenovirus. In vitro, a 10 microM ganciclovir concentration was able to kill 100% of the infected cells. For in vivo experiments, brain tumors were established by stereotactic injection of C6 glioma cells in the caudate nucleus of rats. Five days later, the recombinant adenovirus was inoculated into the tumors and the animals were treated by intraperitoneal injections of ganciclovir for 14 days. At the end of ganciclovir therapy, histological examination revealed a 28-fold decrease in tumor volumes in the treated animals, as compared with control animals. In long-term studies, the mean survival time of the treated animals were four-fold longer than that of control ones. Magnetic resonance imaging demonstrated an apparent complete tumor regression in 62% of the animals. However, late tumor recurrence was observed in the treated animals. Repeated inoculation of C6 glioma cells in the contralateral hemisphere of long-term surviving animals resulted in either tumor rejection or slowly growing tumors. These findings demonstrate the potential efficacy of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration in the treatment of rat gliomas.


Subject(s)
Brain Neoplasms/therapy , Genetic Therapy/methods , Glioma/therapy , Thymidine Kinase/genetics , Adenoviridae/genetics , Animals , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Ganciclovir/therapeutic use , Gene Transfer Techniques , Genes, Viral , Genetic Vectors , Glioma/genetics , Glioma/pathology , Magnetic Resonance Imaging , Male , Rats , Rats, Wistar , Simplexvirus/genetics , Time Factors
18.
J Neurooncol ; 24(3): 259-65, 1995.
Article in English | MEDLINE | ID: mdl-7595756

ABSTRACT

Using a rat C6 brain tumor model, we studied the antitumor effects of Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene transfer followed by ganciclovir treatment. C6 glioma cells were transfected in vitro with the HSV-tk gene, and tested for their sensitivity to ganciclovir. Although there was no surviving cell at a 30 microM ganciclovir concentration, unmodified C6 cells were not affected by the drug. For in vivo experiments, intracerebral tumors were induced in rats by stereotactic injection of 10(4) HSV-tk-modified C6 cells. Ten days later, the animals were treated with intraperitoneal injections of ganciclovir for 21 days. The tumors evolution was evaluated by high resolution magnetic resonance imaging. In 33% of the rats, the signal intensity of the tumors became heterogeneous, with development of highly hyperintense areas, and a complete tumor regression was subsequently noted. Histological examination of successfully treated tumors revealed progressive necrosis with formation of cysts. The survival time of the HSV-tk/ganciclovir treated animals was consistently increased, all rats surviving more than 30 days and 33% of them being still alive after 80 days.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Glioma/drug therapy , Magnetic Resonance Imaging , Simplexvirus/enzymology , Animals , Brain Neoplasms/pathology , Disease Models, Animal , Ganciclovir/therapeutic use , Gene Transfer Techniques , Glioma/pathology , Male , Neoplasm Staging , Neoplasm Transplantation , Rats , Rats, Wistar , Reproducibility of Results , Survival Rate , Thymidine Kinase/genetics , Thymidine Kinase/therapeutic use
19.
Transpl Int ; 7(1): 11-6, 1994.
Article in English | MEDLINE | ID: mdl-8117396

ABSTRACT

In a rat model, the left kidney was subjected to 60 min of normothermic ischemia followed by 15 min of reperfusion, whereas the right kidney, serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n = 12) or University of Wisconsin (UW) solution (n = 6) for 10 min. Each kidney was then harvested and stored at 4 degrees C in its respective solution. After 24 and 48 h of cold storage, the following vasoactive substances were measured in the preservation media: endothelin (ET), angiotensin II (A-II), thromboxane (B2) (TxB2), and prostaglandin I2 (PGI2). After 24 h in EC solution, left kidneys uniformly produced significantly higher concentrations of each vasoactive substance than right kidneys: ET 1.64 +/- 0.3 pg/ml vs 0.82 +/- 0.1 pg/ml (P < or = 0.009); A-II 20.8 +/- 6.2 pg/ml vs 7.75 + 2.3 pg/ml (P < or = 0.007); TxB2 100.8 +/- 17.7 pg/ml vs 40.1 +/- 11.7 pg/ml (P < or = 0.04); PGI2 638.3 +/- 41.1 pg/ml vs 318.3 +/- 36.4 pg/ml (P < or = 0.001), respectively. At 48 h, a similar pattern of results was obtained as the kidney continued to produce TxB2 and prostacyclins during the 24-48 h period. In the UW solution, basal levels of ET and A-II were lower than those in EC solution, but similarly increased after initial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Angiotensin II/analysis , Endothelins/analysis , Ischemia/diagnosis , Kidney Transplantation , Kidney/blood supply , Organ Preservation Solutions , Thromboxane B2/analysis , Adenosine/chemistry , Allopurinol/chemistry , Animals , Cryopreservation , Glutathione/chemistry , Humans , Hypertonic Solutions/chemistry , Insulin/chemistry , Ischemia/metabolism , Kidney/metabolism , Male , Organ Preservation , Radioimmunoassay , Raffinose/chemistry , Rats , Rats, Wistar
20.
Cancer Res ; 53(19): 4715-9, 1993 Oct 01.
Article in English | MEDLINE | ID: mdl-8402649

ABSTRACT

The antitumorigenic effects of endogenous opioid peptides and their presence in extracerebral tumors are well documented. In this study, methionine-enkephaline (met-enkephalin) was measured by radioimmunoassay in 108 glial and nonglial brain tumors and in 44 associated cyst fluids. By immunohistochemistry, the distribution of the peptide and its precursor, preproenkephalin A, was also analyzed. Met-enkephalin and preproenkephalin were detected in the cytoplasm and cell processes of all tumors. Moreover, for neuroectodermal tumors (i.e., gliomas, gangliogliomas, and dysembryoplastic neuroepithelial tumors), a strong inverse correlation (P < 0.0001) was observed between the met-enkephalin levels and the degree of malignancy (242.9, 148.3, 55.3, and 30.3 pg/mg protein for grade 1, 2, 3, and 4, respectively). When compared to normal tissue, this differential expression mainly results from a decrease in the opioid peptide content in high-grade neuroectodermal tumors. Meningiomas and cerebral metastases displayed low met-enkephalin levels, similar to those of grade 4 neuroectodermal tumors. Large amounts of met-enkephalin were found in all cyst fluids. These data suggest that the endogenous opioid system is an integral component of brain tumors and that met-enkephalin may represent a useful malignancy marker in neuroectodermal tumors.


Subject(s)
Brain Neoplasms/chemistry , Brain Neoplasms/pathology , Cysts/chemistry , Cysts/pathology , Enkephalin, Methionine/analysis , Enkephalins/analysis , Glioma/chemistry , Glioma/pathology , Protein Precursors/analysis , Brain Neoplasms/classification , Brain Neoplasms/surgery , Cysts/classification , Cysts/surgery , Glial Fibrillary Acidic Protein/analysis , Glioma/classification , Glioma/surgery , Humans , Immunohistochemistry , Radioimmunoassay
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