It is generally accepted that the accumulation of multiple genetic alterations is essential for development of human tumor. The altered genes can be classified into 5 groups according to their function : (1) cell growth factor and its receptor genes, (2) cell cycle regulator genes, (3) DNA repair genes, (4) genes related to cell invasion and adhesion, (5) genes for angiogenesis. We speculate that at least one out of each group of genes is required for the development of glial tumors. Two different kinds of glioblastomas are proposed, that is, the progression type and the de novo type. The former is believed to be associated with p53 alteration, but the latter is not. The p53 alteration can cause the cell cycle disregulation, failure of DNA repair, impairment of apoptosis induction, acceleration of neovascularization and acquisition of drug resistance. Unexpectedly, the de novo type glioblastomas, which are with wild type p53, show worse clinical course than the progression type glioblastomas. Regarding the de novo type glioblastomas, certain alternative genetic changes other than p53 alteration may act as more adverse factor(s). Recently, it has been shown that the genetic alterations on chromosome 10, such as FGFR2, Mxi-1, PTEN and DMBT1, are frequently seen in glioblastomas. The authors verified that the alteration of FGFR2 was closely associated with unfavorable clinical outcome of the patients with glioblastoma. Thus, genotypic analysis of brain tumors will provide the essential information for selecting the modality of treatment as well as predicting the prognosis.

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Two gene therapy approaches were studied for the treatment of malignant glioma ; a)suicide gene therapy using the herpes simplex virus-thymidine kinase (HS-tk) gene and ganciclovir, and b)immuno-gene therapy using cytokine gene. In the case of suicide gene therapy, Oldfield et al. started it at the National Institute of Health in the USA and reported its safety and efficacy in 1997. In this paper, further developments of gene therapy for brain tumor are summarized, including the development of gene transfer vectors.

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Gene therapy is emerging as a potential strategy for the treatment of cardiovascular disease such as restenosis after angioplasty, vascular bypass graft occlusion, myocardial infarction, transplant coronary vasculopathy, homozygous familial hypercholesterolemia and cystic fibrosis, for which no known effective therapy exists. Gene therapy requires efficient in vivo gene transfer technology. During the past decade, many gene transfer methods including viral transfer techniques have been developed, and some are being applied clinically in human gene therapy studies. Some aspects of the biology and pathophysiology of the cardiovascular system start to emerge, and then the time is ripe for the introduction of gene therapy to the management of cardiovascular disorders. The first FDA approved human gene therapy protocol started on 14 September, 1990 in ADA deficiency patients. Eight years since the first approval, over 200 active clinical studies of gene therapy are under investigation (1997). In the cardiopulmonary field, 6 protocols (transfer of LDL receptor to hepatocytes, CFTR to lung, Vascular endothelial growth factor to ASO and restenosis after PTCA, antisense c-myc to restenosis, E2F decoy to graft failure) have been approved. Their objectives are generally to evaluate 1)in vivo efficacy, 2) safety, and 3) therapeutic efficacy. As gene therapy becomes a therapeutic reality, the following must be addressed : 1) safety, 2) persistence of gene expression and duration of treatment, and 3) regulation. In the future, we must find ideal and suitable promoters that can be regulated but allow expression of sufficient amounts of the product, (e. g., a "cut-off"system) for effective gene therapy. Although there are still many unresolved issues, human gene therapy for cardiovascular disease is now a reality.

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Application of molecular genetics has made it possible to identify genes for many hereditary neurodegenerative diseases, among which triplet repeat diseases have been the focus of interest as a common mechanism for neurodegenerative diseases. Triplet repeat diseases are diseases caused by unstable expansion of trinucleotide repeats in the causative genes. In triplet repeat diseases caused by expansion of CAG trinucleotide repeats, the CAG repeat code for polyglutamine stretches. Recent studies have revealed that the existance of proteins with expanded polyglutamine streches results in aggregate formation and induces apoptosis. Suppression of aggregate formation or apoptosis is expected to bring new avenues for developing therapies for these diseases.

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Although strategies for managing hypertensive cerebellar hemorrhage are fairly standardized, previous analyses have been limited by the use of univariate statistical methods, such as the chi-square test. We retrospectively examined the functional outcome in patients with hypertensive cerebellar hemorrhage using multivariate statistical analysis, and discuss the therapeutic effectiveness of medical and surgical treatment. Among 96 patients with non-traumatic cerebellar hemorrhage, 87 received a diagnosis of hypertensive cerebellar hemorrhage. Clinical data were available from a total of 81 patients who underwent medical therapy (50 cases) or hematoma evacuation after craniectomy (31 cases). In the medical therapy group, a favorable outcome (good recovery or moderate disability) occurred in 72% (36/50), and multivariate analysis showed that the following variables were significantly associated with a favorable outcome : a score of 14-15 on the Glasgow Coma Scale (GCS) at admission ; a maximum hematoma diameter of less than 4cm ; and patent quadrigeminal cistern on CT scan. In contrast, in the craniectomy group, the rate of favorable outcome was 45% (14/31), and variables significantly associated with a favorable outcome according to multivariate analysis included the following : patent quadrigeminal cistern on CT ; a GCS score of 11-15 on admission ; a maximum hematoma diameter of less than 5 cm ; and absence of intraventricular hematoma in the lateral ventricle. We conclude that hematoma evacuation after craniectomy is indicated in patients with a GCS score of 11 to 13 on admission and a maximum hematoma diameter of less than 5 cm, in order to obtain a favorable outcome (good recovery or moderate disability). At present, however, absence of the quadrigeminal cistern on admission CT predicts a very poor outcome in patients with hypertensive cerebellar hemorrhage, even after craniectomy. Accordingly, we suggest that surgical treatment should be performed immediately if partial compression of the peri-brainstem cistern is seen on CT scan, indicating impending brainstem compression.

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We report a case of gonadotropin-producing pituitary adenoma mimicking a tuberculum sellae meningioma. A 59-year-old man was admitted to our department. For 4 years he had complained of recent memory disturbance and hyposmia. Ophthalmological examination revealed a slight superior visual field defect. The remainder of the neurological examination was normal. MR imaging demonstrated a 5×3×3 cm sellar/ suprasellar tumor extending into the frontal skull base as an iso-intense mass with homogeneous enhancement on T1-weighted images. Endocrinological evaluation revealed a high FSH (111.06mIU/ml) but a normal LH level in serum. The presumptive diagnosis was tuberculum sellae meningioma or invasive pituitary adenoma. A bifrontal craniotomy was performed, disclosing a smooth reddish brown mass that was easily dissected from adjacent brain including the pituitary gland. The tumor was totally removed without complications. Histopathological examination revealed a gonadotropin-producing pituitary adenoma. Serum FSH level fell to within normal range.

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The authors present 2 uncommon cases of pituitary lesions that were histologically verified as metastatic cancer. Case 1 : A 48-year-old female had frequent episodes of nausea, vomitting and weight loss. Case 2 : A 67-year-old male was admitted with general fatigue and double vision. MRI demonstrated pituitary lesions in both cases. The patients underwent transsphenoidal surgery, and pathological examinations confirmed metastatic adenocarcinoma in the pituitary gland. Metastatic tumors in the pituitary gland are uncommon and differential diagnosis is sometimes difficult even using modern neuroimaging techniques. The characteristic feature of these uncommon lesions is discussed along with a review of the literature. In this report, the authors demonstrated that dynamic MRI is useful for differential diagnosis between pituitary adenoma and pituitary metastasis.

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Slipping of the lumboperitoneal (LP) shunt system into the peritoneal cavity is a rare but serious complication of this procedure. The authors treated a 12-year-old boy with idiopathic intracranial hypertension who presented with headache and vomiting, and who had undergone LP shunt using the conventional shunt system with ordinary fixture tab. Three days after the operation, the whole system slipped into the abdominal cavity. The second operation of LP shunt was performed using a new silicon fixture device with three small holes. The patient left the hospital 2 weeks after the 2nd operation absent of any neurological symptoms. This new device enables better fixation of the LP shunt system to the lumbodorsal fascia, as compared to the conventional LP shunt system.

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