Clinical Benefits of Antioxidative Supplement Twendee X for Mild Cognitive Impairment: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Prospective Interventional Study.

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.

Cardiovascular events occur independently of high on-aspirin platelet reactivity and residual COX-1 activity in stable cardiovascular patients.

Several studies have indicated that approximately 25 % of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8 %). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients.

Cerebral and spinal cord tanycytic ependymomas in a young adult with a mutation in the NF2 gene.

We studied one frontal lobe tumor and multiple spinal cord tumors (one in an extramedullary location) that had been resected from a 24-year-old man. The frontal lobe tumor was well demarcated and non-infiltrating, and consisted of eosinophilic, elongated fibrillary cells arranged in a fascicular pattern. A similar histology was reproduced in the spinal cord tumors, with additional areas showing standard features of ependymoma. Immunohistochemical and ultrastructural observations revealed that all the tumors were ependymal in nature with positivity for GFAP and epithelial membrane antigen and negativity for oligodendrocyte transcription factor 2, showing intra- and intercellular microrosettes, leading us to a diagnosis of tanycytic ependymoma for the frontal lobe tumor and tanycytic ependymoma with ordinary ependymomatous component for the spinal cord tumors. The spinal extramedullary tumor was a schwannoma. Importantly, a heterozygous truncating mutation in the NF2 gene was identified in the blood lymphocytes from the patient. It is known that multiple nervous system tumors can occur in neurofibromatosis type 2 (NF2), which is caused by mutation in the NF2 gene, and that occurrence of ependymoma, including the tanycytic variant, can be associated with this genetic condition. The present case provides further information about the clinicopathology of tanycytic ependymoma with details of the immunohistochemical, ultrastructural and genetic features.

Platelet function and spontaneous thrombolytic activity of patients with cerebral infarction assessed by the global thrombosis test.

Measurements of platelet reactivity and assessment of the efficacy of antiplatelet drugs are widely recognized as pre-requisite for the diagnosis and treatment of stroke patients. A recently established shear-induced platelet reactivity test using non-anticoagulated blood (the Global Thrombosis Test) has facilitated measurements of physiologically relevant platelet function and thrombolytic activity. 195 healthy volunteers, not taking antiplatelet drugs or anticoagulants, and 185 patients with acute cerebrovascular diseases were enrolled. The effect of antiplatelet drugs on platelet function and thrombolytic activity was assessed using the Global Thrombosis Test after 14 days of medication. The occlusion time (OT), an index of platelet reactivity, in healthy controls was 284.9 ± 92.2 s. The lysis time (LT), an index of thrombolytic activity, in healthy controls was 2,231 ± 1,223 s. Both times had no significant difference between males and females. The OT of all stroke patients was 210.3 ± 140.8 s and was shorter than that of the healthy controls (284.9 ± 92.2, p < 0.0001). The LT of all stroke patients was 3,159 ± 1,549 s and was longer than that of the controls (2,231 ± 1,223, p < 0.0001). Medication significantly prolonged the OT from 184.5 ± 150.6 s (before) to 295.3 ± 208.1 s (after) in all patients, indicating a reversal of the hyper-platelet reactivity. In addition, medication shortened the LT from 3,924 ± 1,718 s (before) to 3,107 ± 1,794 s (after) in all patients. A prothrombotic state exists in stroke patients due to enhanced platelet function and suppressed thrombolytic activity. Medication improved these physiological parameters of haemostasis.

Supratentorial glioblastoma treated with radiotherapy: use of the Radiation Therapy Oncology Group recursive partitioning analysis grouping for predicting survival.

OBJECTIVE: This study aimed to evaluate the usefulness of recursive partitioning analysis model established by the Radiation Therapy Oncology Group for predicting the survival of patients with supratentorial glioblastoma treated with radiotherapy and to determine prognostic factors for the subgroups of this prognostic model. METHODS: A total of 108 glioblastoma patients treated with radiotherapy between January 1987 and December 2005 were retrospectively reviewed. Recursive partitioning analysis classes III, IV, V and VI included 8, 29, 32 and 39 patients, respectively. These classes were divided into two subgroups: a good prognostic group containing classes III-IV and a poor prognostic group containing classes V-VI. The median radiation dose was 60 Gy. Seventy-five patients received chemotherapy and/or immunotherapy. RESULTS: The overall survival differed significantly among classes III, IV, V and VI, with median survival times of 34, 15, 11 and 7 months, respectively. Among the good prognostic group, patients with basal ganglia invasion showed poorer survival outcomes than patients without basal ganglia invasion. Among the poor prognostic group, patients with tumor sizes of <5 cm and patients treated with nimustine hydrochloride showed better survival outcomes than those with tumor sizes of > or =5 cm and those without treatment with nimustine hydrochloride, respectively. CONCLUSIONS: This study confirms the prognostic value of the recursive partitioning analysis grouping. Basal ganglia invasion could be a useful predictive factor for survival in the good prognostic group, whereas tumor size and treatment with nimustine hydrochloride could be useful predictive factors in the poor prognostic group.

Assessment of an ELISA kit for platelet-derived microparticles by joint research at many institutes in Japan.

AIM: Platelet-derived microparticles (PDMPs) play roles in normal hemostatic responses to vascular injury because they possess prothrombinase activity. Although the most widely used method for studying PDMP is flow cytometry, we previously developed an enzyme-linked immunosorbent assay (ELISA) method as an easier and more reproducible PDMP assay. The purpose of this study was to use various clinical settings to verify whether this ELISA method can produce equivalent results to flow cytometry for PDMP. METHODS: We performed a large-scale clinical study for various thrombotic and subatherothrombotic diseases using an ELISA kit. The study group included 692 patients with cerebral infarction, heart failure, acute coronary syndrome or diabetes mellitus. RESULTS: When baseline PDMP values in the various diseases were compared with those in healthy controls, significant differences were noted in all cases. There were significantly elevated levels of PDMPs in diabetic patients with complications but no thrombosis. When baseline PDMP values in cerebral infarction were compared within the subclassifications, atheroma and other types of infarction exhibited significantly elevated PDMP levels compared with lacunar infarction. Cerebral infarction exhibited a significant change in PDMPs after therapy compared with the baseline (before therapy), but not in acute coronary syndrome and heart failure. The ELISA method exhibited results almost identical to flow cytometry for PDMP in various atherothrombotic diseases. CONCLUSION: Although further examinations to evaluate the therapeutic usefulness of these diseases are necessary, ELISA kits possibly represent a new tool for PDMP related to atherothrombosis.

[A case of CNS metastasis from gastric MALT lymphoma].

Recently, the incidence of primary CNS lymphoma (PCNSL) is increasing. Metastatic CNS lymphoma occurs much less than PCNSL. We report the case of a 53-year-old man who presented with CNS metastasis from gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The symptoms at the time of diagnosis were dizziness and aphasia. MRI revealed a left parietal lobe tumor with a large peritumoral edema. About 4 years ago, he had suffered from gastric MALT lymphoma with a high grade component. Eradication of Helicobacter pylori led to remission of the disease 18 months after the treatment. From his past history, the brain tumor was suspected of being a metastatic lymphoma. Stereotactic biopsy revealed diffuse large B-cell lymhoma. Histopathological findings including lymphocytic subsets were almost identical between the primary gastric MALT lymphoma and metastatic brain lymphoma. Complete remission was obtained by repeated high-dose methotrexate chemotherapy. There has been no recurrence for 5 years without additional therapy. This case is probably the first report of CNS metastasis from gastric MALT lymphoma.

Cytologic feature by squash preparation of pineal parenchyma tumor of intermediate differentiation.

Pineal parenchyma tumor of intermediate differentiation (PPTID) is a very rare intracranial tumor, and pathological investigation limited to immunohistological and ultrastructural analyses have been published to date. Although intraoperative cytology is one of the important approaches for initial diagnosis in brain tumors, no or little studies on cellular morphology of PPTID have been demonstrated due to its rarity. We report here cytological features of PPTID obtained from stereotactic surgical specimens in a case of 27-year-old female manifested by dizziness and diplopia. Brain MRI revealed an unhomogeneously enhanced, large-sized tumor (56 x 52 x 60 mm) mainly located in the pineal region expanding from the midbrain to superior portion of the cerebellum and the fourth ventricle. Squash cytology showed increased nucleocytoplasmic ratio, hyperchromatic nuclei, and small rosette-like cell cluster but cellular pleomorphism was mild to moderate and necrotic background was not observed. Histology showed high cellularity, moderate nuclear atypia, and small rosette formation but neither bizarre tumor cells nor necrosis was present. Mitotic counts were very low (less than 1 per 10 high-power fields) and the MIB-1 labeling index was relatively high (10.1%). Tumor cells were immunohistochemically positive for neural markers such as synaptophysin, neurospecific enolase but not for glial fibrillary acidic protein or S-100. In some parts, cells were strongly reactive for neurofilament protein. Taken together, we made a final diagnosis of PPTID. This is the first presentation of cytological analysis by squash preparation that gives an important clue to accurate diagnosis of pineal parenchymal tumor and to understand its malignant potential.

A rare case of malignant glioma suspected to have arisen from a cavernous sinus.

A 55-year-old woman presented with a right trigeminal dysfunction (dysesthesia) initially, followed by right oculomotor and abducens paresis lasting 1 month. Neuroimaging studies showed an enhanced mass in the right cavernous sinus extending to the trigeminal ganglion. The extraparenchymal tumor located around the right trigeminal ganglion was totally removed, except for an intracavernous lesion, by the orbitozygomatic approach. The solid tumor was completely separated from the brainstem and seemed to be a trigeminal schwannoma arising from the trigeminal ganglion or cavernous sinus at surgery. A histological examination, however, found a typical malignant glioma that consisted primarily of astrocytic tumor cells. Immunohistochemical staining showed the tumor cells stained intensely for GFAP, S-100 protein, and vimentin, but not for NFP, Schwann/2E, CD34, and CD68. The mean MIB-1 index was 12.4%. The tumor recurred after a short time, and then it rapidly disseminated into the subarachnoid space and left the cerebral hemisphere. The patient died 1 year after the initial symptoms in spite of aggressive surgery, radiation, and chemotherapy with temozolomide. There are no previous reports of a malignant glioma arising from either the cavernous sinus or the trigeminal ganglion. From the pathogenetic point of view, this malignant glioma is an extremely rare case that developed clinically and neuroradiologically from the cavernous sinus and was suspected be being derived from ectopic glial tissue.

[An adult case of precursor B cell lymphoblastic lymphoma extending from right neck to upper cervical spinal region].

We report the rare adult case of upper cervical spinal tumor diagnosed precursor B cell lymphoblastic lymphoma. A 48- year-old male had suffered from right neck pain and swelling for two months. He had no neurological symptoms. The serum level of IL-2 receptor was high (1,820 U/ml). The radiological examinations including MRI showed the tumor extending from right neck to the epidural space from medulla to the C4 level. The pathological diagnosis of biopsy specimens was malignant lymphoma. Since the early pre-B lymphoblast antigens were positive by the flow cytometry, the diagnosis was precursor B cell lymphoblastic lymphoma. This type of lymphoma is highly aggressive. The intensive chemotherapy regimen such as hyper-CVAD was superior to the lymphoma-like regimens. In the case showed the progressive neurological symptoms such as myelopathy and urinary incontinence, the immediate surgical decompression of the spinal cord may be necessary. Measurement of IL-2 receptor and biopsy with flow cytometry were necessary to work out the treatment strategy of the spinal malignant lymphoma. In this case, the complete response (CR) of the tumor was achieved with hyper-CVAD regimen and radiation therapy.