Superoxide dismutase activity in cisternal cerebrospinal fluid after aneurysmal subarachnoid haemorrhage

It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm. A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically. Mean cisternal CSF level of SOD in 12 control cases (12.99 +/- 2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44 +/- 0.7 U/ml) and in 40 patients treated by delayed surgery (7.64 +/- 0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23 +/- 1.86 U/ml; in 27 cases without vasospasm mean level was 5.43 +/- 0.7 U/ml (p < 001). The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SA

Surgery followed by radiotherapy for the treatment of metastatic epidural spinal cord compression from breast cancer

STUDY DESIGN: Retrospective analysis of breast cancer patients with metastatic epidural spinal cord compression (MESCC) undergoing surgery and radiation therapy. OBJECTIVE: To assess feasibility and clinical outcome of multidisciplinary approach in breast cancer patients with MESCC. SUMMARY OF BACKGROUND DATA: Studies so far published in the setting of surgery and/or radiotherapy in the management of MESCC usually included many malignancies, without considering the different primary histology. However, when looking at prognostic variables of this therapy, histological type comes out as a major determinant of outcome. METHODS: Twenty-three patients with symptomatic MESCC from breast cancer treated between January 2004 and April 2009 were included in this analysis. Twenty-six surgical procedures followed by radiotherapy were performed. Clinical outcome and local recurrence was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scans. Twenty-three cases (88.4%) had back pain before treatment with a visual analog scale score 6 or greater; neurologic deficit (FS A-D) was present in 19 cases (65.5%). RESULTS: Complete remission of pain, lasting until death or progression of disease in another skeletal site, was obtained in 25/26 cases (96.1%). All patients had complete recovery of neurologic deficit. No major morbidity occurred. No patients had recurrence in the site of treatment. Median survival was 36 months (range, 3-60) and overall survival at one, three, and five years was 70%, 42%, and 34%, respectively. CONCLUSION: We provided evidence of surgery and radiotherapy to be feasible with limited morbidity. Clinical outcome has been highly satisfactory in terms of pain and local disease control. The discussion of each case within a multidisciplinary team is of central importance in defining the most appropriate therapeutic approach

Oxidative events in neuronal and glial cell-enriched fractions of rat cerebral cortex

The aim of this work was to investigate how neurons and glial cells separated from rat brain cortex respond to "in vitro" oxidative stress induced by incubation of the cellular fractions in the presence of prooxidant mixtures; in addition, the endogenous enzymatic antioxidant capacity of the purified fractions was investigated. Neuronal and glial cell-enriched fractions were obtained from rat cerebral cortex following passages of the tissue through meshes and centrifugations. The following parameters were evaluated: antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and glucose-6-phosphate dehydrogenase (G6PDH); lipid peroxidation products (TBARS) prior to (basal) and after (iron-stimulated) incubation with a mixture of iron and ascorbic acid; intracellular production of reactive oxygen species (ROS) using a fluorescent probe, dichlorofluorescin-diacetate, in basal, iron-stimulated, and menadione stimulated conditions. SOD and GSHPx activities showed no significant changes between neurons and glia, whereas CAT and G6PDH activities were found to be significantly lower in glia than in neurons. TBARS levels were significantly lower in the glial fraction than in neurons, both in basal and iron-stimulated conditions. ROS production showed no differences between neurons and glia in both basal and menadione-stimulated conditions. Iron-stimulation produced a marked increase in ROS production, limited to the neuronal fraction, with the glial values being similar to the basal ones. Our conclusion is that glia and neurons isolated from rat cerebral cortex show a similar pattern of the most important antioxidant enzymes and of their basal ROS production, whereas glia is more resistant in "oxidative stress" condition

Inactivation of alpha1-antiproteinase (alpha1-AT) and changes in antioxidants plasma levels in subarachnoid hemorrhage

Recent studies have suggested that a quantitative or a qualitative imbalance between the activity of proteases and its inhibitors hypothetically might be involved in intracranial aneurysm rupture. In the present study we test the hypothesis that the systemic reduction of α1-antitrypsin activity might be related to the elevated oxidative potential exerted by cigarette smoking and/or to a systemic low antioxidant capacity. We studied, in a series of 57 patients bearing intracranial aneurysms, the relationship between α1-antitrypsin activity, cigarette smoking and the following variables measured in plasma: vitamin A, vitamin E, thiol groups, urate and lipid peroxide levels. Serum levels of α1-antitrypsin are higher in patients with subarachnoid hemorrhage than in cases of unruptured aneurysms, while the levels of vitamin A and vitamin E are significantly lower in patients that suffered subarachnoid hemorrhage than in controls. Both vitamin A and E levels are related to the occurrence of rupture of the aneurysm, as elicited by logistic regression analysis (P=0.017 and P=0.014, respectively), with a protective effect of higher levels of the variables, as shown by their odds ratio (0.028 and 0.84, respectively). No significant changes in the strength of the association could be appreciated when controlling for smoking habit. None of the other tested variables could be related to the occurrence of the aneurysm rupture. Both α1-antitrypsin serum level and the level of vitamin A appeared to be independently related to α1-antitrypsin collagenase inhibitory capacity percentage (P=0.03 and P=0.025), with no independent influence of the type of aneurysm and the smoking habit. The results of the present study show that the qualitative pattern of α1-antitrypsin is significantly related to the serum level of liposoluble vitamin A, while the type of aneurysm and the smoking habit have no independent influence. This suggests that in a situation in which systemic levels of vitamin A are reduced, the risk of a reduced activity of α1-antitrypsin as controller of proteases is elevated, with the consequent increased risk of aneurysm bleedin

Multimodal approach to the management of metastatic epidural spinal cord compression (MESCC) due to solid tumors

PURPOSE: To assess the impact of a multidisciplinary approach for treatment of patients with metastatic epidural spinal cord compression in terms of feasibility, local control, and survival. METHODS AND MATERIALS: Eighty-nine consecutive patients treated between January 2004 and December 2007 were included. The most common primary cancers were lung, breast, and kidney cancers. Ninety-eight surgical procedures were performed. Radiotherapy was performed within the first month postoperatively. Clinical outcome was evaluated by modified visual analog scale for pain, Frankel scale for neurologic deficit, and magnetic resonance imaging or computed tomography scan. Nearly all patients (93%) had back pain before treatment, whereas major or minor preoperative neurologic deficit was present in 62 cases (63%). RESULTS: Clinical remission of pain was obtained in the vast majority of patients (91%). Improvement of neurologic deficit was observed in 45 cases (72.5%). Local relapse occurred in 10%. Median survival was 11 months (range, 0-46 months). Overall survival at 1 year was 43.6%. Type of primary tumor significantly affected survival. CONCLUSIONS: In patients with metastatic epidural spinal cord compression, the combination of surgery plus radiotherapy is feasible and provides clinical benefit in most patients. The discussion of each single case within a multidisciplinary team has been of pivotal importance in implementing the most appropriate therapeutic approach

Percutaneous vertebral augmentation in metastatic disease: state of the art

Improvements in diagnosis and treatment have prolonged cancer survival, with a consequent increase in the incidence of spinal metastases and vertebral compression fractures with associated axial pain, progressive radiculomyelopathy, and mechanical instability. Pain relief in malignant vertebral compression fractures is key to achieving a better quality of life in patients under palliative care. The gold standard for pain relief is nonsteroidal anti-inflammatory drugs and opioids. Nonresponsive cases are then treated with radiotherapy, which may require 2-4 weeks to take effect and in most cases does not provide complete pain relief. Percutaneous vertebroplasty and percutaneous kyphoplasty can in particular give relief in patients with vertebral body compression fractures that do not cause neurological deficits but severely compromise quality of life because of intractable pain