Clinical assessment of a novel antiadhesion barrier gel: prospective, randomized, multicenter, clinical trial of ADCON-L to inhibit postoperative peridural fibrosis and related symptoms after lumbar discectomy.

A prospective, multicenter, randomized, double-blind, controlled study of ADCON-L Anti-Adhesion Barrier Gel (a medical device by Gliatech Inc, Cleveland, OH) was conducted in 298 patients undergoing first-time lumbar discectomy to evaluate the safety and effectiveness of ADCON-L in preventing postoperative peridural fibrosis and in improving patient clinical outcome. After lumbar discectomy, patients were randomized to receive either ADCON-L gel or nothing (control group) at the conclusion of the surgical procedure. Six months after surgery, peridural scar was evaluated by magnetic resonance imaging, and postoperative pain and straight-leg-raise angle were assessed. No statistically significant differences between the ADCON-L and control groups were observed in terms of adverse events or wound healing characteristics. ADCON-L gel was shown to be safe and to significantly inhibit peridural scar compared with the control group (P = 0.002). That peridural scarring was reduced with ADCON-L gel was further supported by direct visualization of scar tissue at reoperation in both groups. ADCON-L-treated patients had better clinical outcomes than did control patients. The incidence of activity-related pain was significantly reduced (P = 0.013), straight-leg-raise examination scores were significantly improved (P = 0.024 on the operative side and P = 0.015 on the nonoperative side), and ADCON-L reduced low back pain when it was most severe (P = 0.047) and at the end of the day (P = 0.044).

Selective extradural anterior clinoidectomy for supra- and parasellar processes. Technical note.

Removal of the anterior clinoid process (ACP) facilitates radical removal of tumors or radical neck clipping of aneurysms in the supra- and parasellar regions by providing a wide operative exposure of the internal carotid artery (ICA) and the optic nerve and by reducing the need for brain retraction. Over a period of 3 years, anterior clinoidectomy was performed in 40 patients, 30 of whom harbored aneurysms (18 of the ICA and 13 of the basilar artery [one patient had two aneurysms]) and 10 of whom had tumors (four large pituitary tumors, four craniopharyngiomas, and two sphenoid ridge meningiomas). The ACP was removed extradurally in 31 cases and intradurally in nine cases. Extradural clinoidectomy was performed in all cases of pituitary adenoma and craniopharyngioma and in most cases of basilar artery aneurysm. Intradural clinoidectomy was performed in two cases of ICA-ophthalmic artery aneurysm, two cases of ICA-posterior communicating artery aneurysm, two cases of ICA cavernous aneurysm, one case of basilar artery aneurysm, and two cases of sphenoid ridge meningioma. The outcome was satisfactory in all patients, except for one patient who underwent clipping of a basilar tip aneurysm and suffered a thalamic and midbrain infarction. Three patients who underwent extradural clinoidectomy suffered a postoperative diminution of visual acuity or a visual field defect on the side of the clinoidectomy. These deficits may have been caused either by drilling of the ACP or by other operative manipulation of the optic nerve. Cerebrospinal fluid rhinorrhea, which required reoperation, occurred in one patient. The authors' experience suggests that the extradural technique of ACP removal is easier and less time consuming than the intradural one and provides better operative exposure. It can be used routinely in treating lesions in the supra- and parasellar regions.

Symptomatic cerebellar metastasis and late local recurrence of a cauda equina paraganglioma. Case report.

This case report contains a description of a 61-year-old patient who presented with a progressive truncal ataxia 22 years after complete removal of a small paraganglioma of the cauda equina. Magnetic resonance imaging of the neuraxis revealed a large cystic lesion in the cerebellar midline, three small cortical-to-subcortical nodular tumors in the posterior fossa, and local recurrences of the paraganglioma of the cauda equina. Pathological examination showed the cerebellar midline lesion to be a paraganglioma, most likely a metastasis from the cauda equina localization.

Experimental retinal branch vein occlusion in miniature pigs induces local tissue hypoxia and vasoproliferative microangiopathy.

In miniature pigs, retinal veins were experimentally occluded using argon laser coagulation. Microvascular modifications leading to retinal hemorrhages and retinal edema were observed some hours after the occlusion. These lesions resolved progressively within 3 weeks after the occlusion, but in most cases ischemic retinal territories persisted. Preretinal partial pressure of oxygen (PO2) measurements, using double barrelled O2-sensitive microelectrodes, showed that all the ischemic areas were indeed hypoxic. In half of the experiments, preretinal and intravitreal new vessels grew on the ischemic territories. Tissue hypoxia appears to be a key step in triggering neovascularization. However, the critical level of hypoxia was not determined.

Scatter photocoagulation restores tissue hypoxia in experimental vasoproliferative microangiopathy in miniature pigs.

Experimental retinal branch vein occlusion using argon laser photocoagulation in miniature pigs induced the development of ischemic retinal territories associated with preretinal neovascularization. Preretinal partial pressure of oxygen (PO2) measurements on the ischemic territories, using O2-sensitive microelectrodes, established that the ischemic retinal areas were hypoxic. Scatter photocoagulation of these ischemic hypoxic territories restores the local PO2 to the normal values within 2 weeks. Hence, the reported inhibitory effect of photocoagulation on the development of retinal neovascularization could be due to a reversal effect on tissue hypoxia.

Cellular and tumoural heterogeneity of EGFR gene amplification in human malignant gliomas.

It has been demonstrated that the epidermal growth factor receptor (EGFR) gene, the normal human counterpart of the viral erb-B oncogene is amplified and overexpressed in over 50% of human malignant gliomas (HMGs). In the present study, analysis of the immunohistological staining characteristics of 57 HMGs using an anti-EGFR monoclonal antibody (mab) showed positive staining in 65% of the tumours with large cellular and regional differences in staining pattern and intensity. Screening a smaller number of HMGs with molecular hybridization techniques revealed 10/21 glioblastomas (48%) amplified for the gene; of 11 glioblastomas studied by Northern blot hybridization, 7 tumours with gene amplification showed RNA overexpression, the remaining 4 without amplification did not. Regional differences in DNA levels were observed by Southern blot in 2 tumours: in one particular case, amplification and overexpression were found to be localized to one half of a single HMG, the other half showing neither EFGR gene amplification nor overexpression.

Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2.

Transforming growth factor (TGF)-beta 1 is a polypeptide that is assumed to play a fundamental role in the growth of both normal and neoplastic cells. TGF-beta 2 is a closely related polypeptide, originally described as glioblastoma cell-derived T cell suppressor factor (G-TsF) due to its immunosuppressive activity. Expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 was examined in tumor cells and was found to be different in several cell lines and tissues that were tested. Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection. The coordinate expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 in glioblastoma was not paralleled by secretion of both polypeptides as only G-TsF/TGF-beta 2 but not TGF-beta 1 was identified in supernatants of glioblastoma cells. These data provide evidence for a post-transcriptional level of regulation for production of the two forms of TGF-beta. As mRNA for G-TsF/TGF-beta 2 was also identified in fresh surgically removed human glioblastoma tissue, G-TsF/TGF-beta 2 may also be secreted within the tumor in vivo. Unlike glioblastoma, human fetal brain tissues or adult brain specimens studied did not express detectable levels of TGF-beta mRNA. Impaired cell-mediated immunity is an established finding in patients with glioblastoma. Secretion of G-TsF/TGF-beta 2 by tumor cells in vivo may contribute to decreased immune surveillance for tumor development, as well as neovascularization of the tumor tissue.

Diffusion of O2 in the retina of anesthetized miniature pigs in normoxia and hyperoxia.

Intraretinal oxygen tension (pO2) and local electroretinogram (ERG) were simultaneously measured in miniature pigs using double-barreled recess type microelectrodes. Transretinal pO2 profiles were recorded during normoxia and hyperoxia in areas close to (juxta-arteriolar) or far from (intervascular) retinal arterioles. In normoxia, in both areas, the pO2 decreased from the inner retina and the choroid towards the middle of the retina. In the inner retina the gradient of the juxta-arteriolar pO2 profile was steeper than that of the intervascular profile. This characteristic persisted during the breathing of 100% O2. Analysis of the pO2 profiles shows that, even in hyperoxia, the choroid cannot supply O2 to the whole retina. The results also support the conclusions of previous work (Riva, Pournaras and Tsacopoulos, 1986) indicating that in the normal retina it is not the O2 diffusing from the choroid to the retinal arterioles the induces vasoconstriction of these vessels. In the miniature pig this constriction appears to maintain inner retina tissue pO2 at a constant level during hyperoxia. From the pO2 transretinal profiles and previously published choroidal O2 fluxes and pO2 values near retinal vessels an explanatory working hypothesis is formulated according to which O2 consumption (qO2) of the outer retina increases during hyperoxia in the miniature pig.