Evaluation of thermo-triggered drug release in intramuscular-transplanted tumors using thermosensitive polymer-modified liposomes and MRI.

Multi-modal thermo-sensitive polymer-modified liposomes (MTPLs) containing an anticancer drug, MR contrast agent, and fluorescent dye have been investigated as "theranostic" nanodevices that can be used to monitor drug delivery in cancer therapy. Here, we measured the physical characteristics of MTPLs, observed the dynamics of MTPLs in vivo, visualized heat-triggered drug release using MRI, and evaluated the treatment effects of the MTPLs with and without heating. In vitro experiments demonstrated that the MTPLs released drugs at temperatures above 41°C. In vivo MTPLs accumulated in tumor tissue, with the accumulation maximized for 4-12hours. MR signal in the tumor was significantly elevated after mild heating for 15 minutes, indicating release of the contrast agent from the MTPLs was facilitated by heat-triggering. Tumor size after treatment with MTPLs and heating was significantly smaller than those of the control groups. In conclusion, MTPLs with MRI are useful for low-invasive cancer theranostics.

[Unruptured aneurysm arising from fenestration of the horizontal (A1) segment in the anterior cerebral artery: a case report and review of the literature].

Cerebral aneurysms arising from fenestration of the horizontal (A(1)) segment in the anterior cerebral artery (ACA) are very rare. In this paper, we report our case, discuss radiological features, and review previous cases. A 70-year-old male was referred to our hospital presenting with memory disturbance. His unruptured cerebral aneurysm in the A(1) segment was incidentally found by magnetic resonance angiography (MRA). Three dimensional computed tomographic angiography (3D-CTA) demonstrated this aneurysm arising from fenestration of the A(1) segment. Surgical neck clipping was performed via the pterional approach, while sacrificing one pair of the A(1) segment. The patient's post operative course was uneventful. Only 14 cases with an aneurysm arising from fenestration of the A(1) segment have been reported previously. In the present case, 3D-CTA was very useful for finding out where the aneurysm arose from, and we also had to be careful about perforating arteries from the A(1) segment during the surgery.

Relationships between event-related potentials and neuropsychological tests in neurologically healthy adults.

The aim of this study was to investigate the relationship between conventional neuropsychological tests and an event-related potential (P300). Subjects were 118 neurologically normal healthy adults 18-74 years old with no history of neurological, neurosurgical, or psychiatric disorders. We administered a neuropsychological test battery and recorded auditory P300 in all subjects. A significant correlation was seen between P300 latency and age, but not between amplitude and age. While significant negative correlations were apparent between some neuropsychological tests and age and P300 latency, stepwise regression analysis to assess the significance of each factor determined that age alone correlated with P300 latency. We therefore concluded that P300 measurements cannot be replaced by neuropsychological tests; rather, brain function should be evaluated by both methods.

Relationship between cognitive function and regional cerebral blood flow in different types of dementia.

PURPOSE: We assessed relationships between cognitive impairment and regional cerebral blood flow (rCBF) in the different types of dementia. SUBJECTS AND METHODS: Subjects, who included 27 with Alzheimer's disease (AD), seven with frontotemporal dementia (FTD), six with vascular dementia (VaD), and 12 normal controls, were evaluated using the Mini-mental State (MMS), Kana-hiroi Test, an auditory verbal learning test (AVLT), a word fluency test (WFT) and Raven's Coloured Progressive Matrices (RCPM). The rCBF was measured using a three-dimensional stereotaxic ROI template method (3DSRT). RESULTS: In all dementia types, left superior frontal hypoperfusion was demonstrated. In AD and VaD significant CBF reduction also was seen in both angular, temporal, occipital, and precentral, both hippocampi, thalami, and pericallosal regions, and the left lenticular nucleus. MMS, Kana-hiroi Test, and AVLT scores correlated with CBF in all regions. WFT scores were correlated highly with CBF in the left side in frontal, temporal, and angular regions and right and left lenticular nuclei, thalami, and pericallosal regions. RCPM scores correlated with CBF in posterior regions. CONCLUSION: Close coupling was evident between reduced rCBF and cognitive dysfunction in patients with dementia. Use of neuropsychologic tests and rCBF determinations in combination should enhance diagnostic accuracy.

Highly temperature-sensitive liposomes based on a thermosensitive block copolymer for tumor-specific chemotherapy.

Recently, we showed that incorporation of poly[2-(2-ethoxy)ethoxyethyl vinyl ether (EOEOVE)], which exhibits a lower critical solution temperature around 40 degrees C, provides temperature-sensitive properties to stable liposomes. In this study, we applied this thermosensitive polymer for preparation of temperature-sensitive liposomes for tumor-specific chemotherapy with doxorubicin (DOX). We prepared liposomes consisting of PEG-lipid, egg yolk phosphatidylcholine, cholesterol and copoly(EOEOVE-block-octadecyl vinyl ether), which was synthesized as poly(EOEOVE) having anchors for fixation onto liposome membrane. The copolymer-incorporated liposomes were stable and retained DOX in their inside below physiological temperatures. However, they exhibited a significant release of encapsulated DOX above 40 degrees C and released DOX almost completely within 1 min at 45 degrees C. The copolymer-modified liposomes exhibited a long circulating property and biodistribution similar to that of PEG-modified liposomes. The copolymer-modified liposomes loaded with DOX were injected intravenously into tumor-bearing mice. Tumor growth was strongly suppressed when the tumor site was heated to 45 degrees C for 10 min at 6-12 h after injection. However, injection of the liposomes exhibited only slight tumor-suppressive effects as long as mild heating was not applied to the target site. The highly temperature-sensitive properties of the copolymer-incorporated liposomes might contribute to establishment of tumor-selective and effective chemotherapy.

Agraphia with abnormal writing stroke sequences due to cerebral infarction.

A 65-year-old, right-handed man presented with speech and gait disturbances. He was alert and cooperative, showing mild right hemiparesis and sensory disturbance. Spontaneous speech was fluent; object naming, word fluency and reading were fully preserved. Sentence repetition and verbal comprehension were mildly impaired. Writing was slow, hesitant and difficult for both spontaneous writing and dictation. Copying was better, although he had some difficulty in copying letters and also complex figures. Sequences of strokes in forming written characters were abnormal; strokes were formed by piecing together several fragments. Computed tomography and magnetic resonance imaging showed a subcortical infarct in the left frontoparietal region. Characteristics of agraphia resembled 'apractic agraphia' and agraphia may have resulted largely from loss or unavailability of the memory of motor patterns necessary for writing letters.

Usefulness of a cube-copying test in outpatients with dementia.

OBJECTIVE: To clarify whether a quantitatively scored cube-copying test could rapidly assess dementia patients, predicting thier performance in cognitive tests. METHODS: Subjects were 171 outpatients with amnesia who were including 92 with Alzheimer's disease (AD); 59 vascular dementia (VD); 17 frontotemporal dementia (FTD); and three lewy body disease (DLB) and 32 normal healthy subjects. Subjects asked to copy a perspective drawing of a cube. Points of connection and plane-orientation errors were scored using Maeshima's method. The Mini-Mental State Examination (MMSE), an auditory verbal learning test (AVLT), a word fluency test and Raven's Coloured Progressive Matrices (RCPM) were administered. Age, clinical disease severity, symptom duration, specific diagnosis and neuropsychological scores were evaluated for relationships with constructional ability. RESULTS: The cube-copying test showed errors in most dementia patients and 11 of 32 normal subjects. Only three patients each with AD and VD copied correctly, but 11 patients with 17 FTD drew the cube correctly. Numbers of connections completed and plane-orientation errors correlated significantly with MMSE, AVLT, word fluency and RCPM scores. CONCLUSION: The cube-copying test is useful for routine clinical dementia screening, however the test examines only one aspect of cognitive function. While not an alternative to conventional neuropsychological examinations, quantitatively scored cube copying can provide a rough estimate of cognitive dysfunction in dementia patients.