Biomechanics of the C5-C6 spinal unit before and after placement of a disc prosthesis.

The study consists of a biomechanical comparison between the intact C5-C6 spinal segment and the same segment implanted with the Bryan artificial disc prosthesis (Medtronic Ltd., Memphis, TN, USA), by the use of the finite element (FE) method. Our target is the prediction of the influence of prosthesis placement on the resulting mechanics of the C5-C6 spine unit. A FE model of the intact C5-C6 segment was built, employing realistic models of the vertebrae, disc and ligaments. Simulations were conducted imposing a compression preload combined to a flexion/extension moment, a pure lateral bending moment and a pure torsion moment, and the calculated results were compared to data from literature. The model was then modified to include the Bryan cervical disc prosthesis, and the simulations were repeated. The location of the instantaneous center of rotation (ICR) of C5 with respect to C6 throughout flexion/extension was calculated in both models. In general, the moment-rotation curves obtained from the disc prosthesis-implanted model were comparable to the curves obtained from the intact model, except for a slightly greater stiffness induced by the artificial disc. The position of the calculated ICRs was rather stable throughout flexion-extension and was generally confined to a small area, qualitatively matching the corresponding physiological region, in both models. These results imply that the Bryan disc prosthesis allows to correctly reproduce a physiological flexion/extension at the implanted level. The results of this study have quantified aspects that may assist in optimizing cervical disc replacement primarily from a biomechanical point of view.

Multibody modeling of the cervical spine in the simulation of flexion-extension after disc arthroplasty.

This paper presents a three-dimensional (3D) multibody model of the cervical spine implanted with an artificial disc. The model was used to predict prosthesis placement influence on the resulting cervical kinematics in a series of patients. The vertebral tract modeled was the C2-C7, and the vertebral geometries were reconstructed from computed tomography (CT) images. The model was used to simulate the flexion-extension motion of the cervical spine in 10 patients implanted with the Prestige commercial disc prosthesis at a single level. For each patient, a geometrical model of the prosthesis was scaled and included in the multibody model to match the size and positioning of the actual prosthesis, as assessed on post-operative radiographs. Simulations of complete flexion-extension were carried out for each patient, and the main parameters relevant to the motion of the vertebral bodies were calculated and compared to data measured from dynamic post-operative radiographs. At the implanted level, the simulated ranges of motion generally agreed with the measured ones, with an average deviation <2 degrees. In addition, the simulated relative angles between vertebral bodies agreed with the measured ones, with minor average differ-ences of 1.2, 1.8 and 2.1 degrees in full flexion, neutral alignment and full extension, respectively. The cervical kinematics after prosthesis placement was influenced both by the design of the artificial joint and by surgical positioning. Therefore, the model presented can be used both to support pre-operative planning for disc arthroplasty and in the optimization of new prostheses design.

Gene amplification as a prognostic factor in primary brain tumors.

The most reliable prognostic factors for patients with primary malignant brain tumors remain histology, age, and functional status. Management of these individuals might be improved by quantifying pertinent molecular markers. We have measured the gene dosage of the epidermal growth factor receptor (EGFR), mouse double minute 2 (MDM2), and cyclin-dependent kinase 4 (CDK4) genes in a series of brain tumor specimens and correlated their amplification status with standard prognostic factors and survival. Individual tumor DNA was successively hybridized with probes for EGFR, MDM2, and CDK4. The signal was quantified by densitometry, and amplification was defined as gene signal > or = 2 times normal. Survival, age, Karnofsky performance status, and histology were correlated with gene amplification. Nineteen astrocytomas, 20 anaplastic astrocytomas, and 70 glioblastomas had complete data available. Median survival with and without any form of gene amplification was 70.7 and 88.6 weeks, respectively (P = 0.0369). For the EGFR gene alone, those with and without amplification had a median survival of 58.9 and 88.6 weeks, respectively (P = 0.0104). By Cox analysis, only tumor histology (P = 0.04) and Karnofsky performance status (P = 0.0157) were significant independent predictors of survival. Gene amplification by itself was not predictive of survival, even for glioblastomas (P = 0.8249). The lack of correlation between gene amplification and survival for patients with primary malignant brain tumors may be because EGFR, MDM2, and CDK4 are only portions of larger signaling systems. Therefore, the lack of a direct correlation between a single gene and outcome is not entirely unexpected.

Iatrogenic cerebrospinal fluid fistula to the pleural cavity: case report and literature review.

The authors observed one case of an iatrogenic subarachnoid-pleural fistula secondary to the resection of an upper lobe carcinoma of the lung. The clinical presentation was characterized by a sudden deterioration of mental status and level of consciousness immediately after the removal of the thoracotomy chest tube. The diagnosis was substantiated by the demonstration of pneumocephalus by a computed tomographic scan of the head and by the identification of a left T5 nerve root fistula by a postmyelographic computed tomographic scan. The excellent anatomical definition achieved by this modality emphasizes its usefulness in the identification and therapeutic management of these lesions. Operative treatment consisted of the suture ligature of the nerve root and a chest drain. The postoperative course was uneventful, and the outcome was excellent, with the only finding of sensory loss in the T5 nerve root territory. A review of the literature disclosed 11 similar cases, with some differences in the choice of the most appropriate diagnostic procedure and significant differences in the therapeutic options, which were related to the various mechanisms of injury.

Isolation and culture of bovine intracranial arterial endothelial cells.

We report a simple explant technique to isolate and propagate endothelial cells from bovine cerebral arteries. The endothelial nature of the cells was confirmed by the presence of Factor VIII/von Willebrand antigen, the ability to phagocytize low-density lipoprotein, and the ability to be induced to express E-selectin. The lack of expression of the CD11c antigen and the absence of smooth muscle alpha-actin immunofluorescence suggested that the cultures were not contaminated with macrophages or smooth muscle cells, respectively. This technique yields pure cerebral arterial endothelial cell cultures, which will be of value for in vitro investigation of cerebrovascular physiology and disease processes.

Intramedullary epidermoid cyst: preoperative diagnosis and surgical management after MRI introduction. Case report and updating of the literature.

Many patients with spinal tumours of developmental origin do not receive preoperative diagnosis and the surgical management, especially as for capsule resection, is often unplanned. Like other uncommon tumours, the intramedullary epidermoid cyst is often an operative or histological finding. Since magnetic resonance imaging (MRI) introduction, evidence has accumulated that they may be preoperatively suspected. In reporting the case of a young patient with a T3-T4 intramedullary epidermoid cyst, the authors present an overview of the clinical, radiological and surgical aspects of such tumors and review the latest literature in which MRI and microsurgical excision were performed. Despite the introduction of new diagnostic and surgical instrumentation, the preoperative diagnosis and surgical management of such tumours need further discussion.

Cell kinetic studies of human intracranial tumors.

The authors report their experience on cell kinetic studies of intracranial tumors. Three methods have been utilized to measure cell kinetic parameters: flow-cytofluorometry, flow-cytofluorometry and "in vivo" administration of bromodeoxyuridine, the monoclonal antibody Ki-67. The results of these studies are reported and the role of each method is discussed.

Single versus multiple drug therapy in the combined treatment of malignant gliomas. A multicenter study.

The best treatment of malignant gliomas has been considered to be surgery followed by irradiation and chemotherapy with nitrosourea compounds. Our controlled and randomized trial was designed in 1982 to analyze the effectiveness of multiple-drug versus single-drug therapy in patients bearing malignant gliomas. After 3 weeks from surgery and histopathological diagnosis 173 patients were randomly assigned to receive one of the three chemotherapy regimens: CCNU alone, CCNU plus VM-26 or CCNU plus VM-26 plus 5-FU. Radiotherapy was administered whole-brain (40-45 Gy) and coned-down focal (15-20 Gy) irradiation for a total of 60 Gy (1700 rets) in conjunction with the first course of chemotherapy. 150/173 patients are evaluable. Statistical analysis of results shows a better quality of life and survival for patients treated with polychemotherapy using a three drug combination than two drug or single drug therapy (13.8 vs 14.7 vs 18.2 months MST; P less than 0.01) but with a higher incidence of toxicity problems. An analysis of prognostic factors and their distribution in each arm of the protocol will be made in the near future.

Multiple meningiomas: a clinical, surgical, and cytogenetic analysis.

Eight cases of multiple meningiomas were found in our 13-year series of 148 operated meningiomas. The relative frequency, 5.4%, of multiple meningiomas observed is compared with that in the literature. The clinical presentation, surgical results, and diagnostic tools are discussed. Cytogenetic analysis was performed in five patients (eight neoplastic specimens). No specific abnormality for multiple meningiomas was found, but our results point out the different origin of each tumor and exclude cell migration through the subarachnoid space as a pathogenetic factor in multiple meningiomas.

Intra-arterial cisplatin in malignant brain tumors: incidence and severity of otic toxicity.

Intra-arterial (IA) cisplatin is used to treat gliomas with the goal of maximizing drug concentration in the brain while minimizing systemic toxicity. The present study is based on the author's experience with IA cisplatin administration in 12 patients. The primary goal of the study was to document the extent of otic toxicity in these individuals. Hearing was tested clinically and with audiograms, before each IA cisplatin injection. Eight women and four men with a mean age of 39 1/2 years (range 22-61) were treated. Diagnoses included 7 glioblastoma multiformes, 4 anaplastic astrocytomas, and 1 gliosarcoma. Diagnosis was obtained by stereotactic biopsy in four and craniotomy for resection and debulking in eight. The mean number of IA injections per patient was 4.58 (range 3-6). The cisplatin dose was 60 mg/m2 with the average dose of cisplatin per cycle being 116 mg (range 96-130 mg). Eleven patients had the agent administered via the internal carotid and one received it by way of a vertebral artery. Nine of the twelve patients (75%) demonstrated pure tone loss, as measured by audiography, of greater than 15 dB in the higher frequencies range (> or = 3 kHz) bilaterally. One patient became deaf and two others had clinically significant hearing loss. The severity of the auditory damage increased after each administration in each of the cases with clinical abnormality. IA cisplatin may have a role in the treatment of patients with primary malignant brain tumors, but further developments to limit otic toxicity would be of value.

Lumbar canal stenosis: results in 40 patients surgically treated.

Authors present the clinical and neuroradiological characteristics of 40 patients treated for lumbar canal stenosis during a 10 years experience. The usefulness of computed tomography in comparison with myelography and plain X-rays of the spine is stressed. The surgical treatment was wide laminectomy involving one or more levels (two to four) plus an eventual foraminotomy but without discectomy. All patients were followed up and in 85% of cases a reduction of clinical symptoms was observed. Residual symptoms were also present in some of the improved patients, they generally accepted them without great dismay.

Cell-kinetic characteristics of human brain tumors.

The proliferative potential of human brain tumors was investigated, in vivo, using bromodeoxyuridine (BUDR) incorporation and flow cytometry (FCM). Patients with a variety of human brain tumors were preoperatively injected with 250 mg of BUDR intravenously. The cell cycle parameters of most of the specimen were measured within 24 h of sampling. The results show that this method is very practical, fast, and feasible for determining the cell-kinetic parameters of human brain tumors. In this study important kinetic parameters such as the duration of S-phase and the potential doubling time of each tumor were calculated in some samples. Our results show a significant difference in labelling index between meningiomas and gliomas. No difference between benign and anaplastic meningiomas was demonstrated in this limited number of cases. The correlation between the labelling index and the clinical and radiological follow-up of each patient should make the assessment of the prognostic significance of the kinetic evaluation, possible. This method could be a useful aid in the selection of new treatment schedules.

Chemotherapy for malignant gliomas of the brain: a review of ten-years experience.

In recent years, there has been a great improvement in the knowledge of the biological aspects of malignant gliomas of the brain. Conversely, there has been an increase of interest in the multimodal treatment of these tumours. In this review, we have analyzed the results of the several reports which have appeared in the literature that deal with the chemotherapeutic treatment of malignant gliomas. Furthermore, some areas of biological investigation that could have an impact on pharmacological therapy are discussed.

Epidermoid and dermoid tumors.

The authors report their experience in the surgical treatment of intracranial dermoid and epidermoid tumors. These lesions are rare but may, in most of the occasions, be completely resected allowing a complete cure of the patient. The usefulness of the most recent diagnostic tools is discussed and the surgical indications, complications and results are reviewed in comparison to the most significant literature reports.

A study on the biological behavior of human brain tumors. Part I. Arachidonic acid metabolism and DNA content.

The study of proliferative characteristics and biochemical aspects seem to be of great importance in order to define brain neoplastic behavior. The purpose of this study is to verify the existence of any possible correlation between Arachidonic Acid (AA) metabolism and proliferative characteristics in 30 meningiomas and 30 neuroepithelial tumors. The most represented metabolite in neuroepithelial tumors is TxB2, while 6-Keto-PGF1 alpha is the lowest represented product. Unimodal DNA distribution was observed in 66% of neuroepithelial tumors and in 87% of meningiomas. Aneuploidy was more frequent in glioblastomas and anaplastic meningiomas as previously reported; AA overall synthesis capacity and profile were similar between unimodal and bimodal cases of neuroepithelial tumors. Total AA metabolite, as well as TxB2 and PGD2, synthesis capacity are significantly higher in cases with S-phase cell percentage greater than or equal to 3% than in cases with S-phase % less than 3%. Total production of AA metabolites via the cyclooxygenase pathway is significantly higher in meningiomas with bimodal DNA distribution than in cases with unimodal DNA content; when considering S-phase cell percentage, similarly to what observed in neuroepithelial tumors, meningiomas with S% greater than 3% shows a significantly higher overall synthesis capacity for AA. AA metabolism capacity well correlates with proliferative patterns in neuroepithelial tumors: the relationship depends preferentially on TxB2 and PGD2 synthesis capacity. In cases of meningiomas, the amount of AA metabolites seem to be related to DNA content and proliferative activity when anaplastic features are histologically demonstrated.

A study on the biological behavior of human brain tumors. Part II: Steroid receptors and arachidonic acid metabolism.

The significance of steroid receptors (SR) in human brain tumors is presently a field of intense investigation in order to clarify some aspects of the biological behavior of these neoplasms. We studied the relationship between the presence of steroid receptors and the production of metabolites of the arachidonic acid cascade which have been reported to have a role in the biological behavior of some human tumors. We found that some metabolites of arachidonic acid are produced in different amounts in brain tumors which either did or did not express some steroid receptors. In particular the PGE2 were higher in estrogen receptors (ER) positive meningiomas than in ER negative ones and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin, is significantly higher in androgen receptors (AR) negative meningiomas than in AR positive ones. In neuroepithelial tumors the glucocorticoid receptors (GR) positive cases synthesized more TxB2 and less PGE2 than the GR negative ones. Our data seem to suggest that some correlations exist between the presence of some steroid receptors and arachidonic acid metabolite production.

Hormonal modulation of brain tumour growth: a cell culture study.

Tissue samples derived from two neuroepithelial tumours and five meningiomas were obtained at surgery from seven patients and cultured in order to study the effect of dexamethasone (DEX) and testosterone acetate (TA) on cell proliferation. Glucocorticoid and androgen receptors (GR, AR) were determined both on tissue samples (7 cases) and on five out of the seven cell cultures obtained by tumours. GR and AR were present respectively in 5 and in 4 out of the tumour specimens assayed and in 4/5 and 2/3 of the tested cell cultures. DEX activity on cell growth was tested on six cell cultures. Four of them showed a significant growth inhibition at the highest drug concentration. On the contrary, a significant growth stimulation was observed in four out of the five cultures, where GR were present, using low hormone concentrations. Treatment with pharmacological doses of TA caused a significant cytotoxicity in all the tested cultures. Low TA concentrations inhibited cell growth in one out of the two cell cultures which contained AR, but were ineffective in cultures lacking AR. Our preliminary results suggest a possible role in growth regulation by DEX and TA in intracranial tumours, on the basis of the presence of specific hormone receptors.