Experience with Photodynamic Therapy Using Indocyanine Green Liposomes for Refractory Cancer.

We reported the development of an effective cancer treatment using a multidisciplinary treatment, including photodynamic therapy (PDT) with indocyanine green (ICG) liposomes and a combination of Lentinula edodes mycelia (LEM) and hydrogen gas inhalation therapy. ICG liposomes were prepared by adding 5 mg of ICG to 50 mL liposomes. Later, 25 mL of ICG liposomes were diluted with 250 mL of 5% glucose solution and administered intravenously to the patient. We selected the multi-laser delivery system (MLDS), a laser irradiator for performing PDT. Further, the patients received a combination of LEM and hydrogen gas inhalation therapy throughout the treatment. We reported two cases of PDT therapy, one with middle intrathoracic esophagus carcinoma and the other with hypopharyngeal cancer. In the first case, the MLDS laser was directly attached to the endoscope and directed to the cancer area with wavelengths of 810 nm. After the treatment, a biopsy demonstrated no tumor recurrence. In the second case, the patient was treated with endovascular PDT using ICG liposomes and MLDS fiber optics. Later, tumor shrinkage was demonstrated after the first round and disappeared after six months. In conclusion, the present findings suggest that the effect of PDT using ICG liposomes with LEM and hydrogen gas may eradicate cancer without burdening patients by enhancing tumor immunity.

Linked alterations in gray and white matter morphology in adults with high-functioning autism spectrum disorder: a multimodal brain imaging study.

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder.

Altered network topologies and hub organization in adults with autism: a resting-state fMRI study.

Recent functional magnetic resonance imaging (fMRI) studies on autism spectrum condition (ASC) have identified dysfunctions in specific brain networks involved in social and non-social cognition that persist into adulthood. Although increasing numbers of fMRI studies have revealed atypical functional connectivity in the adult ASC brain, such functional alterations at the network level have not yet been fully characterized within the recently developed graph-theoretical framework. Here, we applied a graph-theoretical analysis to resting-state fMRI data acquired from 46 adults with ASC and 46 age- and gender-matched controls, to investigate the topological properties and organization of autistic brain network. Analyses of global metrics revealed that, relative to the controls, participants with ASC exhibited significant decreases in clustering coefficient and characteristic path length, indicating a shift towards randomized organization. Furthermore, analyses of local metrics revealed a significantly altered organization of the hub nodes in ASC, as shown by analyses of hub disruption indices using multiple local metrics and by a loss of "hubness" in several nodes (e.g., the bilateral superior temporal sulcus, right dorsolateral prefrontal cortex, and precuneus) that are critical for social and non-social cognitive functions. In particular, local metrics of the anterior cingulate cortex consistently showed significant negative correlations with the Autism-Spectrum Quotient score. Our results demonstrate altered patterns of global and local topological properties that may underlie impaired social and non-social cognition in ASC.

Specific feature of olfactory dysfunction with Alzheimer's disease inspected by the Odor Stick Identification Test.

AIM: Alzheimer's disease (AD) is one of the most significant diseases associated with ageing. As the disease progresses, symptoms including olfactory dysfunction often appear along with cognitive dysfunction. We examined olfactory and other indexes to investigate correlations between them and the validity of an olfactory test for screening for AD. METHODS: To assess whether odorant identification will be a useful diagnostic tool, we investigated the olfactory ability of Alzheimer's disease patients (ADs) using the Odor Stick Identification Test for the Japanese. As a control, we compared ADs to aged people without AD or dementia. To investigate the relationship between olfactory loss and severity of AD, we used the Mini-Mental State Examination, Alzheimer's Disease Assessment Scale, biomarkers in spinal fluid and single-photon emission computed tomography as brain imaging. RESULTS: In comparing the controls and ADs, we believe that there are significant differences, with ADs having particularly low activity with regard to olfactory function and some odorants. We showed that there was a definite correlation between cognitive and olfactory function. To confirm this, we sorted subjects by markers of severity scores for comparison. In all areas, the AD group had more serious olfactory dysfunction, including in the early stages of AD. CONCLUSION: This study suggests that olfactory tests such as the Odor Stick Identification Test for the Japanese can be useful for assessing severity of AD, including cognitive dysfunction. Further investigations will enable us to establish an olfactory assessment method for the screening or diagnosis of AD.

Touch Panel-type Dementia Assessment Scale: a new computer-based rating scale for Alzheimer's disease.

BACKGROUND: The Alzheimer's Disease Assessment Scale (ADAS) was designed as a rating scale for the severity of dysfunction in the cognitive and non-cognitive behaviours that are characteristic of persons with Alzheimer's disease. Its subscale, the ADAS-cog, is a cognitive testing instrument most widely used to measure the impact of the disease. However, the ADAS-cog takes more than 45 min to administer and requires a qualified clinical psychologist as the rater. A more comprehensive rating battery is therefore required. In the present study, we developed a computerized test battery named the Touch Panel-type Dementia Assessment Scale (TDAS), which was intended to substitute for the ADAS-Cog, and was specifically designed to rate cognitive dysfunction quickly and without the need of a specialist rater. METHODS: The hardware for the TDAS comprises a 14-inch touch panel display and computer devices built into one case. The TDAS runs on Windows OS and was bundled with a custom program made with reference to the ADAS-cog. Participants in the present study were 34 patients with Alzheimer's disease. Each participant was administered the ADAS-cog and the TDAS. The test scores for each patient were compared to determine whether the severity of cognitive dysfunction of the patients could be rated equally as well by both tests. RESULTS: Pearson's correlation coefficient showed a significant correlation between the total scores (r= 0.69, P < 0.01) on the two scales for each patient. The Kendall coefficients of concordance obtained for the three corresponding pairs of tasks (word recognition, orientation, and naming object and fingers) showed the three TDAS tasks can rate symptoms of cognitive decline equally as well as the corresponding items on the ADAS-cog. CONCLUSIONS: The TDAS appears to be a sensitive and comprehensive assessment battery for rating the symptoms of Alzheimer's disease, and can be substituted for the ADAS-cog.

Effect of aromatherapy on patients with Alzheimer's disease.

OBJECTIVE: Recently, the importance of non-pharmacological therapies for dementia has come to the fore. In the present study, we examined the curative effects of aromatherapy in dementia in 28 elderly people, 17 of whom had Alzheimer's disease (AD). METHODS: After a control period of 28 days, aromatherapy was performed over the following 28 days, with a wash out period of another 28 days. Aromatherapy consisted of the use of rosemary and lemon essential oils in the morning, and lavender and orange in the evening. To determine the effects of aromatherapy, patients were evaluated using the Japanese version of the Gottfries, Brane, Steen scale (GBSS-J), Functional Assessment Staging of Alzheimer's disease (FAST), a revised version of Hasegawa's Dementia Scale (HDS-R), and the Touch Panel-type Dementia Assessment Scale (TDAS) four times: before the control period, after the control period, after aromatherapy, and after the washout period. RESULTS: All patients showed significant improvement in personal orientation related to cognitive function on both the GBSS-J and TDAS after therapy. In particular, patients with AD showed significant improvement in total TDAS scores. Result of routine laboratory tests showed no significant changes, suggesting that there were no side-effects associated with the use of aromatherapy. Results from Zarit's score showed no significant changes, suggesting that caregivers had no effect on the improved patient scores seen in the other tests. CONCLUSIONS: In conclusion, we found aromatherapy an efficacious non-pharmacological therapy for dementia. Aromatherapy may have some potential for improving cognitive function, especially in AD patients.

Sugar chains of cerebrospinal fluid transferrin as a new biological marker of Alzheimer's disease.

BACKGROUND/AIMS: Alzheimer's disease (AD) is a well-known type of dementia. However, it remains difficult to identify AD in the early stage and to distinguish it from other dementing disorders. We examined glycoproteins in cerebrospinal fluid (CSF) as potential biological markers of AD. METHODS: CSF samples were collected from AD, other dementia and nondemented patients. Glycoproteins in CSF were detected by lectin blotting using wheat germ agglutinin (WGA), and sugar chain analysis was performed by isoelectric focusing. RESULTS: In Alzheimer's CSF, several glycoproteins had lower WGA-binding activities, one of which was sufficiently sensitive and specific to distinguish AD from nondemented controls and other dementias. Further analysis identified this glycosylated protein as transferrin, and altered sugar chain composition of transferrin isoforms was observed despite normal protein levels in CSF. CONCLUSION: The decreased WGA-binding activity of transferrin in AD is probably due to altered glycosylation of transferrin molecules. Transferrin glycosylation is thus a potential biological marker for AD diagnosis, and changes in this glycosylation may play an important role in the pathophysiology of AD.