Discrepancy between Preoperative Imaging and Postoperative Pathological Finding of Ruptured Intracranial Dissecting Aneurysm,and Its Surgical Treatment: Case Report

The choice of therapeutic strategy for intracranial dissecting aneurysm is often based on radiographic features, including characteristic geometry (e.g., irregular stenosis, segmental stenosis, aneurysm formation [pearl-and-string sign]), irregular fusiform or aneurysmal dilation, double lumen, and tapering occlusion. However, there is often a discrepancy between preoperative radiographic data and actual dissecting length. The present report describes three cases in which there was a discrepancy between preoperative radiographic data and actual dissecting length in patients undergoing direct trapping with or without revascularization. All three cases experienced good outcomes, but these cases underscore the fact that open surgery is a good option for management of ruptured intracranial dissecting aneurysms for determination of the rupture point, dissecting length, and the relationship between dissecting area and small arteries arising from the associated vessel.     

Successful diuretics treatment of protein‐losing enteropathy in Noonan syndrome

There are few reports on successful high‐dose spironolactone treatment of refractory protein‐losing enteropathy (PLE) caused by Fontan procedure. We report successful diuretics treatment with spironolactone and furosemide at standard dose, of refractory PLE in a patient with Noonan syndrome and repaired congenital heart disease. This is the first successful application of diuretics treatment in a patient with refractory PLE without Fontan procedure. This case illustrates that diuretics treatment can be the first‐line treatment of PLE regardless of the causative physiology, and can be effective in refractory PLE with Noonan syndrome.     

Gradual deterioration of brainstem cavernous angioma associated with hemophilia--case report

A 49-year-old man presented with a brainstem cavernous angioma associated with hemophilia manifesting as gradual progression of neurological deficits over a period of 2 weeks. Computed tomography revealed a hematoma and perifocal edema on the left side of the pons, and T(2)-weighted magnetic resonance imaging revealed a hemosiderin rim around the lesion with venous malformation. The neurological deficits deteriorated despite conservative treatment, so surgery was performed 2 weeks after admission, after supplementary therapy of factor IX. The hematoma and anomalous vascular component were entirely removed without intractable bleeding. The postoperative course was uneventful and his neurological symptoms improved. The histological diagnosis was cavernous angioma. Six months after onset, he was doing well. Surgery can be effective for the treatment of hemorrhagic cavernous angioma associated with hemophilia after initiation of supplementary therapy with coagulation factor.     

Malignant transformation of oligoastrocytoma: a case report

We report a case of oligoastrocytoma resembling dysembryoplastic neuroepithelial tumor (DNT) with malignant transformation. A 35-year-old woman presented with headache and generalized convulsion in May 2003. Magnetic resonance imaging (MRI) revealed an extensive left temporal lobe tumor. She underwent partial resection of the tumor under awake surgery, while preserving her language function. The surgical specimen showed that the majority of the tumor was composed of a glioneuronal element. However, there was also an abundant oligoastrocytoma component. Therefore, our first pathological diagnosis was oligoastrocytoma and DNT. She then underwent radiation therapy. The tumor recurred at the left temporal lobe in June 2005. She then underwent open biopsy. The pathological diagnosis was anaplastic oligoastrocytoma with a MIB-1 staining index of 79%. She received PAV (procarvazine, ACNU, and vincristine) chemotherapy, and the tumor subsided transiently. However, she died 3 years after the first operation. Although the histological findings of the first surgical specimen closely resembled those of DNT, radiologic findings and clinical course were different from those of DNT. The authors concluded that this tumor could be a malignant transformation of oligoastrocytoma mimicking DNT, and we wish to give warning that the presence of a glioneuronal component is not an absolute benign hallmark.     

Reduction of 5-fluorouracil (5-FU) gastrointestinal (GI) toxicity resulting from the protection of thymidylate synthase (TS) in GI tissue by repeated simultaneous administration of potassium oxonate (Oxo) in rats

Purpose: An important cytotoxic effect of 5-fluorouracil (5-FU) is the inactivation of thymidylate synthase (TS) (EC 2.1.1.45) activity by the formation of a ternary complex consisting of covalently bound 5-fluorodeoxyuridine 5′-monophosphate (FdUMP), TS and 5,10-methylenetetrahydrofolate (CH₂FH₄). The gastrointestinal (GI) toxicity of 5-FU is also caused by its phosphorylation in the GI tract. Potassium oxonate (Oxo) competitively inhibits pyrimidine phosphoribosyltransferase (EC 2.4.2.10), which converts 5-FU to 5-fluorouridine 5′-monophosphate (FUMP) in vitro. In this study the benefits of combining Oxo and tegafur (FT), which is a masked compound of 5-FU, in reducing the GI toxicity of 5-FU and in protecting the activity of TS in the normal GI tissues were evaluated. Methods: We administered orally a preparation of 1 M FT and 0.4 M 5-chloro-2,4-dihydroxypyridine (CDHP) with or without 1 M Oxo (called S-1 and FT + CDHP, respectively) or vehicle only (control) to rats for ten consecutive days and compared the toxicity, the histopathological findings and the free TS activity in the GI tissues of the treated rats. Results: During the experimental periods, the signs of toxicity, such as a decrease in body weight, diarrhea and death, were only observed in the rats treated with FT + CDHP. The histopathological findings in the ileum and colon samples from rats treated consecutively with S-1 on day 1, day 4, day 7 and day 10 were less frequent and more mild than in the samples from rats treated with FT + CDHP. Furthermore, the free TS activities in the ileum samples of rats given S-1 and FT + CDHP were significantly decreased compared with the activity in samples from the control rats throughout the experimental periods. The free TS activities in GI tissues of rats treated with S-1 were higher than the TS activities in tissues from rats treated with FT + CDHP daily from day 4 to day 10, although activities in S-1-treated rat were decreased to almost same low levels as in FT + CDHP-treated rats on day 1. Conclusions: Our results suggest that repeated simultaneous administration of Oxo and FT can effectively protect the activity of TS by decreasing FdUMP via FUMP from 5-FU in GI tissue, and may lead to a reduction in GI toxicity. Received: 13 August 1999 / Accepted: 24 February 2000     

Lipophilic fraction of Panax ginseng induces neuronal differentiation of PC12 cells and promotes neuronal survival of rat cortical neurons by protein kinase C dependent manner

Panax ginseng is a traditional Chinese herb with a wide range of therapeutic benefits. Recent studies focusing on its effect on the central nervous system have revealed that ginseng has neurotrophic effects including differentiation of neurons. However, most studies involve use of the water-soluble fraction called saponin, and little is known about the effect of the lipophilic fraction. In the present study, we have shown that the lipophilic fraction of ginseng at a concentration of between 0.1 and 50 μg/ml can induce neurite outgrowth of PC12 cells in a dose-dependent manner. Nearly all cells showed morphological differentiation in response to the lipophilic fraction. This morphological differentiation of PC12 cells appeared to be similar to that of NGF. The lipophilic fraction of ginseng also induced neurite extension and promoted survival of rat cortical neurons at a concentration of between 0.025 and 1 μg/ml. These neurotrophic effects on PC12 cells and cortical neurons were not inhibited by K252b, which selectively blocks neurotrophin actions by inhibiting trk-type receptor tyrosine phosphorylation. This suggests that trks do not participate in the neurotrophic action of the lipophilic fraction. However, the effects were completely attenuated by sphingosine, polymyxin B or staurosporin, known inhibitors of protein kinase C (PKC) and calmodulin-dependent kinases. Our results suggest that the lipophilic fraction of ginseng exerts its neurotrophic effects via PKC-dependent pathways.     

Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G polymorphism in Japanese patients with type 1 diabetes

Interleukin-18 (IL-18) is a potent proinflammatory cytokine which is strongly associated with the development of diabetes in NOD mice. To test the putative involvement of IL-18 gene polymorphism in predisposition to human type 1 diabetes, the SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of IL-18 gene were analyzed by sequence-specific PCR in 116 patients with type 1 diabetes and 114 normal controls. A linkage disequilibrium found only three of the four possible haplotypes defined by these SNPs. The distribution of the IL-18 gene genotypes at position -607 was significantly different between patients with type 1 diabetes and normal controls (P=0.023). Furthermore, there was a significant increase in haplotype 1 (-607C/-137G) in the patients compared with controls (P=0.006). The association study of the susceptible CTLA-4 genotype (GG at nucleotide position 49 in exon 1) or HLA-DR4-DQB1*0401 and type 1 diabetes showed that the predisposing IL-18 gene haplotype modulates the risk on CTLA-4 GG genotype, but not on HLA-DR4-DQB1*0401 haplotype. Among subjects carrying the CTLA-4 GG genotype, the frequency of IL-18 haplotype 1 in patients with type 1 diabetes was significantly higher than that in controls (91% vs. 71%, P=0.012). However, IL-18 haplotype 1 was not frequent in patients who do not exhibit the CTLA-4 high-risk genotype. These results suggest that the IL-18 gene polymorphism is associated with a type 1 diabetes susceptibility, and there might be a gene-gene interaction between IL-18 gene with susceptible CTLA-4 gene.