Combined treatment of ruptured aneurysm accompanied by intraventricular hemorrhage; neuroendoscopy and coiling: case report.

Subarachnoid hemorrhages with intraventricular hemorrhage (IVH) have been treated with aneurysmal clipping and ventricular drainage. We present a combined treatment with coiling and endoscopy: coiling of the ruptured distal anterior cerebral artery aneurysm and neuroendoscopic removal of IVH.

Long-term follow-up of 5 patients with intracranial germinoma initially treated by chemotherapy alone.

BACKGROUND: High rates of overall- and event-free survival have been reported in patients with intracranial germinoma treated by radiotherapy. We report the long-term results after treatment initially with chemotherapy, but without radiation. PATIENTS AND METHOD: Five patients with an intracranial germinoma were treated with 2 cycles of etoposide and cisplatin, without radiotherapy. All achieved complete remission; 3 suffered recurrence within 2 years and were again treated with 2 cycles of etoposide and cisplatin followed by radiotherapy. RESULTS: At long-term follow-up, each of the 5 patients was in complete remission without further recurrence. Each patient with a neurohypophyseal germinoma who presented with endocrinopathy had initially recovered endocrinological function. CONCLUSION: In a patient with a germinoma chemotherapy, and restriction of radiation to those with recurrence may allow restoration of hypophyseal function damaged by the intracranial germinoma without compromising long term survivial.

Venous congestion is a major cause of neurological deterioration in spinal arteriovenous malformations.

OBJECTIVE: Although venous congestion is considered to be a major cause of progressive myelopathy in patients with spinal dural arteriovenous fistulae (DAVFs), the neurological deterioration in patients with spinal intradural arteriovenous malformations (AVMs) has been attributed to hemorrhage or to vascular steal. To reexamine this theory, we analyzed our own cases of spinal vascular diseases. METHODS: In 24 patients with spinal vascular diseases, those who demonstrated progressive myelopathy with T2 hyperintensity in the spinal cord on magnetic resonance imaging (MRI) were diagnosed as patients with congestive myelopathy. We further examined the clinical courses, MRI findings, and reversibility of these cases. RESULTS: Venous congestion was judged to be a cause of neurological deterioration in 13 patients (7 DAVFs, 6 intradural AVMs). The T2 signals on these patients' MRI scans were located in the center and extended over several levels not corresponding to distribution of ischemia due to arterial steal. Of the patients who were diagnosed with congestive myelopathy, no differences between those with DAVFs and those with intradural AVMs were apparent in terms of clinical manifestations and reversibility. Eight (four DAVFs, four intradural AVMs) of 13 patients experienced neurological improvement after treatment. All patients with poor outcomes had intervals from onset of more than 3 years and showed contrast enhancement of the spinal cord on MRI studies. CONCLUSION: Spinal intradural AVMs as well as spinal DAVFs can be a cause of venous congestive myelopathy. Regardless of its etiology, congestive myelopathy is potentially reversible if properly diagnosed and treated.

Induction of apoptosis in glioma cells: an approach to control tumor growth by blocking basic fibroblast growth factor autocrine loop.

Glioma is a group of neoplasms derived from neuroepithelial tissue. High grade glioma is characterized by the presence of mitotic figures and the occurrence of vascular endothelial hyperplasia. This article reviews the effects of growth factors which are secreted by glioma cells on the proliferative activity of both glioma cells and vascular endothelial cells. Among various glioma-derived growth factors, we have found that basic fibroblast growth factor (bFGF) plays an important role in determining malignant trait of human glioma via its autocrine loop. Furthermore, we discuss candidate molecular targets for the therapy of high-grade glioma by blocking the autocrine loop of bFGF.

Repression of human fibroblast growth factor 2 by a novel transcription factor.

Here we describe the cloning of the regulator of fibroblast growth factor 2 (FGF-2) transcription (RFT) using a yeast one-hybrid screening with a defined motif in FGF-2 promoter as a target sequence. Overexpression of human RFT (RFT-A) reduces FGF-2 RNA and protein levels in both normal and tumor cell lines. Its splice variants, RFT-A' and RFT-B, have deletions in the putative DNA binding domain and fail to bind FGF-2 promoter and repress FGF-2 gene expression. The ratios of RFT isoforms differ between normal and tumor cells, with the splice variants dominating in tumor cells. Overexpression of RFT-A induces glioma cell death. Our data suggest that regulation of FGF-2 by RFT is important for cellular functions and may be impaired in certain tumors.

Apoptosis of human glioma cells in vitro and in vivo induced by a neutralizing antibody against human basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) is mitogenic to neuroectoderm- and mesoderm-derived cells and is a potent angiogenic factor. Abundant amounts of this factor and its receptor are detected in human glioma tissues and cells, and bFGF in glioma is thought to be involved in autonomous cell growth as an autocrine growth factor. A neutralizing mouse monoclonal antibody (MAb) against bFGF, 3H3 MAb, has been shown to inhibit both in vitro and in vivo growth of human glioma cell lines. This study shows that the human glioma cell lines U-87MG and U-251MG, which express high levels of bFGF and its receptor, can be induced to undergo apoptosis when cultured with 3H3 MAb. It is also demonstrated that 3H3 MAb can cause apoptosis in the same glioma cells that were transplanted into nude mice. Furthermore, enforced overexpression of bcl-2 protein by gene transfection prevented 3H3 MAb-induced apoptosis of glioma cells. It is concluded that induction of apoptosis by the neutralizing antibody is a promising therapeutic strategy for glioma.

Transcriptional regulation of basic fibroblast growth factor gene by p53 in human glioblastoma and hepatocellular carcinoma cells.

Mutations of the p53 gene are found in various human cancers. The frequency of its mutation is reported to increase during tumor progression in most tumors. In human gliomas, mutations of the p53 gene are found in about one-third of the malignant forms and in few of the benign ones, indicating their possible involvement in tumor progression. On the other hand, we have recently shown that basic fibroblast growth factor (basic FGF) plays a crucial role in tumor progression as an autocrine growth factor in tissues of human gliomas. Therefore, we hypothesized that p53 might regulate the promoter activity of the basic FGF gene, which has several GC boxes and no typical TATA box. In this study, cotransfection assays using human glioblastoma and hepatocellular carcinoma cells and establishment of stable cell lines expressing mutant-type p53 were performed. The basic FGF gene promoter was demonstrated to be regulated by p53 at the transcriptional level and its basal core promoter was found to be responsive to p53. Expression of endogenous basic FGF was also demonstrated to be activated by mutant type p53. Wild-type p53 repressed gene expression of the basic FGF and its mutant activated it in vitro, implying one of the possible pathways in tumor progression.

Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues.

We examined the expression of fibroblast growth factor receptor-1 (FGFR-1), namely FLG, in tissues of 18 human gliomas, 10 human meningiomas, 3 human metastatic brain tumors, and 2 normal human brains by means of immunohistochemistry. All tissues were positively stained for FGFR-1. Primary brain tumors were more abundantly immunoreactive than normal brain tissues (Mann-Whitney U test, P < 0.05). There was significant correlation between the expression level of basic fibroblast growth factor (basic FGF) and that of FGFR-1 in tissues of human glioma (Spearman's test, P < 0.05). The expression level of FGFR-1 of tumor cells increased in correlation with that of endothelial cells in glioma tissues (Spearman's test, P < 0.001). We previously reported that basic FGF is produced in more than 90% of human glioma and meningioma tissues. Together with these data, it is suggested that basic FGF is involved in autonomous cell growth and tumorigenesis of gliomas and meningiomas as an autocrine growth factor in vivo.

[Ruptured dissecting aneurysm of the vertebral artery missed by initial angiography; case report].

Dissecting aneurysm of the intracranial arteries is a well known clinical entity, and its angiographic findings are also well recognized. We encountered a case with dissecting aneurysm of the vertebral artery presented with subarachnoid hemorrhage (SAH). The initial angiography was normal but repeated angiography demonstrated a dissecting aneurysm. This case is reported here, and the relevant literature is reviewed. A 46-year-old woman had been well until she complained of headache. She was admitted to a local hospital and found to have SAH. She was transferred to our clinic for further examination. On admission the patient was drowsy but able to be aroused. Her neurological state was normal except for a mildly stiff neck. Computed tomography (CT) demonstrated massive SAH in the basal cistern and intraventricular hemorrhage in all ventricles. CT also demonstrated acute hydrocephalus. Four-vessel cerebral angiography was performed using transfemoral catheterization. No definite abnormalities, except for a small aneurysm in the cavernous portion of the right internal carotid artery, were found. Because aneurysm in the cavernous portion could not cause SAH, we could not define the origin of the SAH. However, retrospectively, a slightly irregular wall of the left intracranial vertebral artery was evident. Repeated angiography performed 28 days later revealed aneurysmal dilatation of this left vertebral artery. Double density of the contrast material was found in the aneurysmal dilatation. Retention of the contrast medium was also seen in the late capillary phase. From these angiographic findings, the aneurysm was diagnosed as being a dissecting aneurysm. Direct surgical attack on the vertebral aneurysm was performed via a left suboccipital craniectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Primary malignant lymphoma in the sphenoid sinus with orbital apex syndrome; a case report].

Only 2.0-6.8% of extranodal malignant lymphomas are found in the nasal region and paranasal sinuses. Primary malignant lymphoma of the paranasal sinuses usually occurs in the maxillary or ethmoid sinuses, and is very rare in the sphenoid sinus. Here we report a rare case of primary malignant lymphoma of the sphenoid sinus that was found accompanying orbital apex syndrome. The patient's progressively deteriorating neurological condition was improved after surgery via the transsphenoidal approach. A 52-year-old man was admitted with reduced left visual acuity, diplopia, and retroorbital pain. CT showed an isodense mass in the sphenoid sinus with slight enhancement, and MRI showed that the lesion was slightly hypointense on T1-weighted images, hypointense on T2-weighted images, and slightly enhanced by Gd-DTPA. On January 19, 1989, the patient suddenly became blind. An operation via the transsphenoidal approach was done as an emergency procedure to decompress the sphenoid sinus and the left optic canal. The histological diagnosis was non-Hodgkin's lymphoma of the diffuse large cell type (B cell lymphoma). Malignant lymphoma in the paranasal sinuses is usually biopsied and treated by chemotherapy and/or radiotherapy without surgical resection. In this rare case, an operation via the transsphenoidal approach was effective in improving the patient's visual acuity.