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Toshihiko Iwamoto

Publications and source records attributed to Toshihiko Iwamoto.

At least 19 recordsLinked to original sources
PubMed2006

Intranuclear immunolocalization of 14-3-3 protein isoforms in brains with spinocerebellar ataxia type 1.

Immunolocalization of 14-3-3 protein isoforms, one of the interacters with ataxin 1, was investigated in spinocerebellar ataxia type 1 (SCA 1) brains using isoform-specific antibodies. Samples from the pons and from the cerebellum of four SCA1 cases and three controls were studied. The intensity of the immunoreactivity (IR) and its subcellular topography were analyzed. In control subjects, granular immunoreactivity for an epitope common to all known isoforms of 14-3-3 proteins (14-3-3 COM) found in the cytoplasm of some pontine and dentate nucleus neurons was weak. It was observed in some Purkinje cells, while its intensity varied. Many nuclei of those neurons and Purkinje cells of SCA1 were intensely immunopositive for 14-3-3 COM, while it was less in their cytoplasm. Expanded polyglutamine epitope was colocalized to 14-3-3 COM epitope in some pontine neurons, sometimes accumulated in intranuclear inclusion-like structures. This findings support previous reports that 14-3-3 proteins stabilize mutant ataxin 1 in nucleus and possibly lead to neurodegeneration. However, nuclear localization of 14-3-3 proteins in SCA1 brains was dependent on its isoforms, i.e. pontine neurons intensely positive for beta, Purkinje cells for tau and dentate nucleus neurons for both, while all of those neurons were consistently positive for zeta isoform, although sigma isoform tended to be located in the cytoplasm. Nuclear accumulation and isoform- and region-dependent subcellular localizations of 14-3-3 proteins may be related to SCA1 pathology, which exhibits marked regional variability.

14-3-3 Proteins↗
PubMed2006

Phenylephrine and pilocarpine eye drop test for dementia with Lewy bodies and Alzheimer's disease.

Pupillary response test using dilute phenylephrine, a sympathetic agonist, and dilute pilocarpine, a cholinergic agonist, were performed in 24 patients with dementia with Lewy bodies (DLB), 40 patients with Alzheimer's disease (AD), and 23 normal elderly subjects. The mydriatic response to 0.5% phenylephrine was significantly greater in the DLB group than in the AD and control groups. The mydriatic change correlated inversely with the reduction in cardiac 123I-metaiodobenzylguanidine uptake. In contrast, miotic response to 0.0625% pilocarpine was significantly greater in the DLB and AD groups than in the control group. The pupil assay using combined phenylephrine and pilocarpine eye drop test may be useful in the detection of patients with DLB and AD and in distinguishing between them.

3-Iodobenzylguanidine↗
PubMed2006

Differentiation of dementia with Lewy bodies from Alzheimer's disease using Mini-Mental State Examination and brain perfusion SPECT.

To determine whether combined studies of Mini-Mental State Examination (MMSE) and brain single photon emission CT (SPECT) would provide more useful means of differentiating between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), we studied 36 patients with probable DLB and 96 patients with probable AD. DLB patients had significantly better performance on word recall, but more impaired attention and copying than AD patients. We confirmed that a weighted score derived by Ala et al. [Ala, T.A., Hughes, L.F., Kyrouac, G.A., Ghobrial, M.W., Elble, R.J. The Mini-Mental State exam may help in the differentiation of dementia with Lewy bodies and Alzheimer' disease. Int J Geriatr Psychiatry 2002;17:503-9]: (Attention-5/3.Memory+5.Construction), was helpful in discriminating between DLB and AD. SPECT study revealed that medial occipital perfusion significantly decreased in DLB patients than AD patients. Combined studies of MMSE and brain SPECT achieved a high discrimination between DLB and AD with a sensitivity of 81% and a specificity of 85%, suggesting that there is a useful and practical approach to differentiate DLB from AD. Our findings will need to be substantiated in an independent and prospective study sample.

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PubMed2006

The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis of Lewy body disease in patients with dementia in a memory clinic.

Reduction in cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake is a characteristic feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and is useful in distinguishing them from other neurodegenerative disorders. The aim of this study was to investigate the role of this method of scintigraphy in the differential diagnosis of dementia in our Memory Clinic. We performed MIBG scintigraphy in patients with dementia referred to the Memory Clinic and compared the heart-to-mediastinum (H/M) ratio of MIBG uptake. Thirty out of 32 patients with DLB and all 9 PD with dementia patients had reduced H/M ratios, whereas 37 out of 40 patients with Alzheimer's disease had normal H/M ratios. Most patients with vascular dementia, frontotemporal dementia, and other dementias had normal H/M ratios. The overall sensitivity to positively identify patients with Lewy body disease (including DLB and PD with dementia) was 95%, and the specificity to distinguish them from patients with other types of dementias was 87%. MIBG scintigraphy showed a high sensitivity for the detection of Lewy body disease, and also a high specificity for discrimination from other types of dementia. The scintigraphy may provide a valuable and adjunctive method in the diagnosis of Lewy body disease and a differential diagnostic tool for patients with dementias.

3-Iodobenzylguanidine↗
PubMed2006

MR features of the substantia innominata and therapeutic implications in dementias.

We measured the thickness of the substantia innominata using magnetic resonance imaging in 122 patients with Alzheimer's disease (AD), 31 patients with dementia with Lewy bodies (DLB) and 34 patients with vascular dementia (VaD), and examined the correlates of cognitive response to donepezil. Although all dementia groups showed significant atrophy of the substantia innominata compared to 28 age-matched controls, atrophy was greater in the DLB group, but less in the VaD group than the AD group. Mini-Mental State Examination score changes at 12 weeks after donepezil administration inversely and significantly correlated with the thickness of the substantia innominata in patients with AD (n=103, r=-0.43, p<0.0001) and in patients with DLB (n=24, r=-0.57, p<0.01), but not in patients with VaD (n=12, r=-0.22, p>0.1). There may be some differences in cholinergic impairment among AD, DLB and VaD, reflecting cholinergic neuropathology. Clinical response to cholinergic therapy may be partly attributable to damaged cholinergic neurons in AD and DLB, but not in VaD, suggesting differences in the therapeutic implication of cholinergic system degeneration.

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PubMed2006

Functional interactions between entorhinal cortex and posterior cingulate cortex at the very early stage of Alzheimer's disease using brain perfusion single-photon emission computed tomography.

OBJECTIVE: The cause of the reduced regional cerebral blood flow (rCBF) in the posterior cingulate cortex in the early stage of Alzheimer's disease has not been clarified. In Alzheimer's disease, the posterior cingulate cortex itself shows little neuropathologic degeneration, and a hypothesis explaining such a discrepancy is that the functional impairment in the posterior cingulate cortex reflects remote effects caused by degeneration in distant but connected areas, such as the entorhinal cortex. To test the hypothesis, we investigated the functional connectivity between the entorhinal cortex and posterior cingulate cortex. METHODS: Sixty-one patients with probable Alzheimer's disease at a very early stage and 61 age-matched healthy controls underwent both brain structural magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). Voxel-based morphometry was performed on MRI data to identify clusters of significantly reduced grey matter concentration in patients with Alzheimer's disease relative to controls, which were set as volumes of interest (VOIs) for correlation analyses of SPECT images. We then used adjusted rCBF values in the VOIs as covariates of interest in statistical parametric mapping. RESULTS: Voxel-based morphometry demonstrated a significant reduction in grey matter concentration in the bilateral entorhinal cortex in Alzheimer's disease. A positive correlation between rCBF in the entorhinal cortex as VOI and that in the limbic and paralimbic systems, including the posterior cingulate cortex, anterior cingulate cortex, lingual gyri and left middle temporal gyrus (P<0.001), was observed in Alzheimer's disease. Control subjects also showed a similar correlation in the limbic and paralimbic systems, but not in the posterior cingulate cortex. CONCLUSION: These results indicate that rCBF changes in the posterior cingulate cortex may be closely related to those in the entorhinal cortex in patients with Alzheimer's disease, thereby supporting the 'remote effect' hypothesis.

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PubMed2006

SPECT follow-up study of cerebral blood flow changes during Donepezil therapy in patients with Alzheimer's disease.

BACKGROUND AND PURPOSE: Treatment with acetylcholinesterase inhibitors (AchEIs) is beneficial for patients with Alzheimer's disease (AD). But the clinical response varies. Functional neuroimaging techniques might allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. We attempted to evaluate the possible correlation between regional cerebral blood flow (rCBF) differences in patients with AD and response to donepezil hydrochloride (Donepezil) therapy. METHODS: The subjects of this study were 51 consecutive patients with AD receiving Donepezil who underwent SPECT at baseline and 10-14 months later. We divided the patients into stabilized (n = 19) and nonstabilized (n = 32) subgroups based on changes in the Mini Mental State Examination (MMSE) score. Analysis of single-photon emission computed tomography (SPECT) data was done using 3-dimensional stereotactic surface projections (3D-SSP) and the stereotactic extraction estimation (SEE) method. We compared differences in rCBF between the two subgroups at baseline and follow-up, and between the baseline and follow-up in each subgroup. RESULTS: Significant correlation was recognized between the mean Z score changes of the left frontal lobe, left limbic lobe, and MMSE change. There were no significant baseline differences in rCBF in any region of the brain between the two subgroups. At the study endpoint, the nonstabilized subgroup showed lower rCBF in the lateral and medial frontal lobes, limbic lobe, lower lateral temporal lobe, and cingulate gyrus compared to the stabilized subgroup. Both patient groups showed a significant post-treatment increase over baseline values in the frontal lobe, and the stabilized group had more extensive and intense increases in the lateral and medial frontal lobes and orbital surface. CONCLUSIONS: Our study suggests that the diversity of clinical responses to Donepezil therapy in patients with AD is associated with rCBF changes, mainly in the frontal lobe. SPECT may be a promising tool to assess the impact of AchEI therapy on the brain function of patients with AD.

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PubMed2006

[The efficacy and adverse effects of rituximab with CHOP or THP-COP in old-old and extremely old patients with diffuse large B cell lymphoma].

AIM: We examined the efficacy and adverse effects of rituximab with CHOP (cyclophosphamide, doxorubicin, vincristin, prednisone) or THP-COP (pirarubicin, cyclophosphamide, vincristin, prednisone) in previously untreated old-old and extremely old patients with diffuse large B cell lymphoma (DLBCL). METHODS: Subjects were 13 initial DLBCL patients consisting of 7 men and 8 women with a median age of 79 years (range 75-91 years). These patients received CHOP or THP-COP plus 375mg/m2 rituximab intravenously given on the day before each cycle. The dose was adjusted depending on the patient's age and associated complications. Administration was performed for 6 to 8 cycles, whenever possible. RESULTS: Seven patients (54%) achieved a complete response (CR), 4 (31%) achieved a partial response (PR), 2 (15%) failed to respond. The 2-year survival rates were 62%. The CR rate and survival rate were higher than in patients previously treated with CHOP alone in our hospital, but there was no statistically significant difference. The most frequent adverse effect was bone marrow suppression, observed in 9 patients (69.2%). Adverse effects that seemed to be infusion reaction occurred in 4 patients (30.7%). These adverse effects related to infusion reaction disappeared by reducing or stopping rituximab. Four (30.7%) patients died and 3 of those died due to disease progression. One of those died 1.5 month after he began chemotherapy and the cause of death was unknown. CONCLUSION: This result suggested that both CHOP and THP-COP combined with rituximab were safe and effective for old-old and extremely old patients.

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PubMed2005

Comparative value of brain perfusion SPECT and [(123)I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer's disease.

PURPOSE: Both decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer's disease (AD). METHODS: The study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[(123)I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections. RESULTS: Medial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT. CONCLUSION: MIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.

3-Iodobenzylguanidine↗
PubMed2005

The prediction of rapid conversion to Alzheimer's disease in mild cognitive impairment using regional cerebral blood flow SPECT.

Mild cognitive impairment (MCI) comprises a heterogeneous group with a variety of clinical outcomes and they are at risk for developing Alzheimer's disease (AD). The prediction of conversion from MCI to AD using the initial neuroimaging studies is an important research topic. We investigated the initial regional cerebral blood flow (rCBF) measurements using single photon emission computed tomography (SPECT) in individuals with 76 amnesic MCI (52 subjects converted to AD and 24 subjects did not convert to AD at 3-year follow-up) and 57 age- and gender-matched controls. We sought functional profiles associated with conversion to AD, then evaluated the predictive value of the initial rCBF SPECT. As compared with controls, AD converters demonstrated reduced blood flow in the bilateral parahippocampal gyri, precunei, posterior cingulate cortices, bilateral parietal association areas, and the right middle temporal gyrus. Non-converters also demonstrated significant reduction of rCBF in the posterior cingulated cortices and the right caudate nucleus when compared to controls. As compared with non-converters, converters showed reductions of rCBF in the bilateral temporo-parietal areas and the precunei. The logistic regression model revealed that reduced rCBF in the inferior parietal lobule, angular gyrus, and precunei has high predictive value and discriminative ability. Although a cross-validation study is needed to conclude the usefulness of rCBF SPECT for the prediction of AD conversion in individuals with MCI, our data suggest that the initial rCBF SPECT studies of individuals with MCI may be useful in predicting who will convert to AD in the near future.

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PubMed2005

Differentiation of dementia with Lewy bodies from Alzheimer's disease using brain SPECT.

We compared regional cerebral blood flow (CBF) patterns in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) using single photon emission computed tomography (SPECT) and investigated the diagnostic utility of SPECT study in differentiating between DLB and AD. SPECT data on 20 patients with DLB and 75 patients with AD were analyzed using three-dimensional stereotactic surface projections. Regional CBF reduction was determined by quantitative analysis using stereotactic extraction estimation method. The DLB group showed a significant CBF reduction in the temporoparietal, frontal lobe and posterior cingulate, similar to the CBF pattern in the AD group, but regional CBF in the medial and lateral occipital lobes decreased significantly in patients with DLB compared with patients with AD. Receiver operating characteristic analysis revealed that regional CBF measurement of the medial occipital lobe, including the cuneus and lingual gyrus, yielded a sensitivity of 85% and a specificity of 85% in discriminating DLB from AD. Objective and quantitative CBF measurement in the medial occipital lobe may be useful in the clinical differentiation of DLB and AD.

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PubMed2005

Prognostic implications of swallowing ability in elderly patients after initial recovery from stroke.

BACKGROUND: It remains unclear how swallowing assessment can help clinicians to predict the risk for pneumonia in elderly persons after ischemic stroke. A prospective case-control study was conducted to evaluate the prognostic utility of swallowing ability assessments. METHODS: Participants were 136 elderly persons who had an acute ischemic stroke 3-12 months previously. They were separated into four groups based on their history of repeated episodes of pneumonia in combination with swallowing ability: Group 1 had neither repeated pneumonia nor swallowing abnormality (n = 69); group 2 had repeated pneumonia but no swallowing abnormality (n = 0); group 3 had swallowing abnormality but no repeated pneumonia (n = 54); and group 4 had both swallowing abnormality and repeated pneumonia (n = 13). The follow-up period was as long as 2.2 years. Outcomes and causes of death were compared among the groups. RESULTS: During the study, the overall mortality rate was higher in group 3 (24 deaths, 44.4%) and group 4 (9 deaths, 69.2%) than in group 1 (3 deaths, 4.3%, both p <.05). The annual mortality rate from pneumonia was also significantly higher in group 3 (21.2%) and group 4 (38.2%) than in group 1 (0.8%, p <.0001). The odds ratio for patients who subsequently died of pneumonia was 46.8 between groups 1 and 3. CONCLUSIONS: The high sensitivity (.96) and specificity (.68) of swallowing ability indicate that the method is useful for identifying those persons at greatest risk for pneumonia and death after ischemic stroke.

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PubMed2005

Aspiration and infection in the elderly : epidemiology, diagnosis and management.

Aspiration of the oropharyngeal or gastric contents by elderly persons often leads to lower respiratory tract infections, such as aspiration pneumonia or pneumonitis. The existence of dysphagia and aspiration in elderly patients are important factors in the occurrence of aspiration pneumonia, but are not sufficient to cause aspiration pneumonia in the absence of other risk factors. Salivary flow and swallowing can eliminate Gram-negative bacilli from the oropharynx in healthy persons. However, elderly persons may have diminished production of saliva as a result of medications and oral/dental disease, leading to poor oral hygiene and oropharyngeal colonisation with pathogenic organisms. When dysphagic patients aspirate pathogenic bacteria while swallowing food or liquids, they must also have decreased defences, such as impaired immunity or pulmonary clearance, in order to develop aspiration pneumonia.Elderly patients with cerebrovascular disease often have dysphagia that leads to an increased incidence of aspiration. It was previously reported that patients with silent cerebral infarction affecting the basal ganglia were more likely to experience subclinical aspiration and an increased incidence of pneumonia. Basal ganglia infarction leads to the impairment of dopamine metabolism and, as a consequence, a decrease of substance P in the glossopharyngeal nerve and sensory vagal nerves. Therefore, dysphagia and a decreased cough reflex may be induced by the impairment of dopamine metabolism in some elderly patients with cerebrovascular disease, suggesting that pharmaceutical agents which modulate dopamine metabolism may be able to improve swallowing and the cough reflex in patients with basal ganglia infarction. The main strategy for controlling aspiration and aspiration-related pulmonary infection in the elderly is to prevent aspiration of pathogenic bacteria along with the oropharyngeal or gastric contents. Because aspiration pneumonia in the elderly is related to certain risk factors, including dysphagia and aspiration, effective preventive measures involve various approaches, such as pharmacological therapy, swallowing training, dietary management, oral hygiene and positioning.

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PubMed2005

Autoimmune hemolytic anemia in an elderly patient with primary Sjögren's syndrome.

Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary glands and lacrimal glands. The histological features of chronic inflammation in primary Sjögren's syndrome may be associated with B cell hyper-reactivity. This syndrome also has various manifestations associated with other exocrine glands and nonglandular tissues. The hematological abnormalities usually seen in Sjögren's syndrome are lymphopenia, leucopenia, and thrombocytopenia. Although the direct Coomb's test is often positive, the occurrence of autoimmune hemolytic anemia (AIHA) is rare. Here, we report an elderly patient with primary Sjögren's syndrome who developed AIHA during the clinical course.

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PubMed2005

[Treatment of bedsores--combination of therapies depended the experimental design method].

The treatment of bedsores is a particular problem in geriatric medicine. We selected standard drugs that may be effective for the decubitus ulcer, and investigated combination therapy to develop efficient treatment The subjects were 16 patients in whom the grade of the bedsore was evaluated as II to IV according to the Shea's depth classification. Treatment was performed while all patients were on air mats. We selected drugs and treatment methods based on the previously established experimental design of Taguchi. Based on this, we created and adapted 16 different component combination treatment programs in accordance with the L16 rectangular cross table. The following component factors were adopted: A: types of covering substances on the wound surface (Elase ointment, isodine sugar, isodine gel solcoseryl ointment); B: Isalopan powder; C: Spray of 10 ml physiological saline containing 500 microg of prostaglandin (concentration 0.005%); D: daily number of treatments; and F: presence or absence of tapping. We serially measured the wound surface area as an index of the speed of wound healing, and measured the interval (day) until the area decreased to one half of the original size (T1/2, half life). We analyzed data on one combination treatment each in 16 patients. Analysis of variance of the above factors showed significant F values for factors A, B, D and F. The contribution rates for factors A, B, D and F were 37.84%, 8.47%, 14.98% and 13.81%, respectively. The error term (e) was 16.37%. Optimal results were seen in the groups in which solcoseryl ointment had been applied twice a day. In this study, prostaglandin, which had been anticipated to be effective, did not show any effects. The error term (e) suggests the presence of other healing factors including individual differences. Concerning this point, it well be necessary to examine a larger number of patients in the future. With ointment treatment alone, without using an air mat, it was confirmed that bedsore area reduction was extremely unstable. Decompression of the affected part may be a basic prevention factor and essential treatment of bedsores.

Actihaemyl↗