Classification of delusions in Alzheimer's disease and their neural correlates

Background: Previous findings on neural correlates of delusion in Alzheimer's disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single‐photon emission computed tomography data. Methods: We selected AD patients with delusions from our consecutive outpatients from 2004 to 2010. In this study, eight types of delusions were evaluated with Neuropsychiatric Inventory and classified by factor analysis. Twenty‐five of the patients also had single‐photon emission computed tomography data, which we used to assess the relationships between cerebral regions of hypoperfusion and hyperperfusion and each classified delusion. The relations were assessed using Statistical Parametric Mapping with normalization to the white matter cerebral blood flow. Results: The delusions were classified into three factors. Factor 1 consisted of a belief that his/her house is not his/her home, phantom boarder symptom, delusion of abandonment, and belief that one's spouse or others are not who they claim to be. Factor 1 was related to hypoperfusion in the right temporal pole and hyperperfusion in the medial frontal and precentral regions. Factor 2 consisted of delusion relating to the television and delusion of persecution. Factor 2 was related to hypoperfusion in the precuneus and hyperperfusion in the insula and thalamus. Factor 3 consisted of delusion of abandonment and delusional jealousy. Factor 3 was related to hypoperfusion in the right inferior temporal and frontal regions and hyperperfusion in the middle frontal gyrus, insula and posterior cingulate gyrus. Delusion of theft was not included in any factors, and it was related to hypoperfusion in the bilateral thalami and left posterior cingulate gyrus and hyperperfusion in the left inferior frontal regions and anterior cingulate gyrus. Conclusions: Delusions in AD were classifiable, and each classified delusion was related to different neural networks.     

Psychometric properties of the Caregiving Burden Scale for Family Caregivers with Relatives in Nursing Homes: Scale development

Aim: Most family caregivers continue their caregiving for frail relatives after admitting them to long‐term care facilities. The characteristics of this caregiving differ from those related to caregiving in home‐care settings. Thus, a new tool to evaluate the burden of family caregivers in institutional settings is needed. The aim of this study was to develop a new scale, the Caregiving Burden Scale for Family Caregivers with Relatives in Nursing Homes, and to confirm its validity and reliability. Methods: We conducted two cross‐sectional questionnaire surveys. The participants were a convenience sample of family members of residents in seven nursing homes for the validation study and in three nursing homes for the test‐retest study in Japan. Statistical analyses examined exploratory/confirmatory factor analyses, internal consistency, concurrent/discriminate validity, and test‐retest reliability. Results: A four‐factor solution with 16 items was selected as the most interpretable questionnaire. In the confirmatory factor analysis, the indices of fitness highly supported these results. The Cronbach's alpha coefficient for the total score was 0.86 and varied between 0.77 and 0.87 in the four domains. The scale showed moderate correlation with the Nursing Home Hassles Scale, suggesting its concurrent validity. The four domains had only a medium correlation with each other, indicating discriminate validity. Conclusions: The developed scale has acceptable validity and reliability for measuring the caregiving burden of family members with relatives in Japanese nursing homes. Future studies using the scale might lead to the improvement of care for family members with relatives in a long‐term care setting.     

Epidemiology and prognosis of subungual melanoma in 34 Japanese patients

The incidence of malignant melanoma is much lower in the Japanese than in Caucasians. However, amongst the various types of malignant melanoma, the subungual and periungual sites are commonly found in the Japanese. One hundred and fifty-one cases of cutaneous malignant melanoma were seen over a 25-year period at our hospital. We found that. In 34 patients (23%). the subungual region was involved, a high frequency for one institution. We have analysed these patients and looked at their treatment. The finger nails were affected in 21 cases (62%) and the toe nails in 1 3 cases (38%). The thumb nails or great toe nails were at tecled in 25 of the 34 patients (73%). In 25 patients, histopathological features of acral lentiginous melanoma were found, with four cases of superficial spreading melanoma and five of nodular amelanotic melanoma. Of the latter group, four mimicked tibrous histiocytic tumour, and one was a desmoplastic malignant melanoma. I he proportion of patients presenting with stage III disease decreased after 1982. with a corresponding increase in patients whose tumour thickness was less than 4 mm (stage II). Concurrently, the prognosis for subungual malignant melanoma improved. The 5-year survival rate in each of the periods 1969–82 and 1981—93 was 5 3 and 87%. respectively. This is similar to that found in plantar malignant melanoma and is fell to be due to a greater public awareness of the condition and to the introduction of effective chemotherapy (the DTIC-AC nitro surear vincristine (OAV) regimen). Although the frequency of malignant melanoma is rather low in the Japanese, our data indicate that there is a high incidence of subungual malignant melanoma. Public awareness of the early stage of malignant melanoma seems to have improved prognosis.     

氨氯地平抑制大鼠脑膜与[~3H]伊拉地平结合的密度(英文)

目的:研究硝苯地平、氨氯地平和( )SM-6586预处理过的大鼠脑膜与[~3H]伊拉地平观察结合密度的变化.方法:用大鼠脑膜,该脑浆膜与硝苯地平(10 nmol L~(-1)),氨氯地平(1μmol L~(-1)),SM-6586(1 nmol L~(-1))以及不加拮抗剂分别预保温45 min,离心,所得沉淀用缓冲液清洗,3次后与[~3H]伊拉地平一起保温,通过Scatchard解析求出用钙拮抗剂预处理后膜成分的K_d和B_(max)值.结果:硝苯地平对[~3H]伊拉地平取代位置的拮抗可以通过清洗而减弱,特殊取代显示出很低的值.但通过氨氯地平和SM-6586拮抗后,在同样条件下拮抗不易被减弱.以上这些药物的K_d值都没有明显的变化.结论:氨氯地平和SM-6586对脑膜中钙通道拮抗的分解过程是缓慢的.     

Effects of FK506 on an experimental model of colitis in rats

Aim: To assess the effects of FK506, a newly developed immunosuppressant, on experimental colitis in rats. Methods: Experimental colitis was induced by a single colonic instillation of hapten 2,4,6-trinitrobenzene sulphonic acid (TNB) in anaesthetized rats. Rats received 30 mg TNB dissolved in 0.25 mL of 50% ethanol, and were sacrificed on day 5 following 4 days dosing with FK506 (0.25, 0.5, 1.0, 2.0 mg/kg, s.c.) or vehicle. Mucosal prostanoid concentrations were determined using high performance liquid chromotography. Tissue myeloperoxidase activities were measured. The effects of FK506 on superoxide radical formation by neutrophils in both rats and humans were also estimated in vitro. Results: Administration of FK506 significantly reduced the colonic damage in a dose-dependent manner. Activities of myeloperoxidase and concentrations of 6-keto-prostaglandin Fl_1α (6-keto-PGF_1α, PGF_2α and PGE₂ in colonic tissue increased significantly following induction of experimental colitis, however, FK506 did not affect these changes. FK506 reduced stimulant-induced superoxide radical formation by neutrophils in rats and humans. Conclusion: FK506 decreased superoxide radical generation by neutrophils, which might contribute to the lessening of colonic damage in this model.     

Severe autoimmune hemolytic anemia associated with IgM warm auto‐antibodies in primary Sjögren’s syndrome

Primary Sjögren’s syndrome is an autoimmune disorder involving mainly salivary and lachrymal glands. However, many extraglandular symptoms have also been reported. Although leucocytopenia and lymphocytopenia are frequently observed in hematological disorders, autoimmune hemolytic anemia is rarely reported. We experienced a case of primary Sjögren’s syndrome developing severe autoimmune hemolytic anemia. The patient’s red blood cells showed spontaneous agglutination in saline at room temperature, and immunoglobulin M (IgM) was detected on the surface of red blood cells by flow cytometry, indicating that autoimmune hemolytic anemia was caused by warm reactive IgM antibodies. Immediate corticosteroid therapy resulted in a dramatic recovery. We report a first case of severe autoimmune hemolytic anemia caused by warm reactive IgM antibodies in primary Sjögren’s syndrome.     

The Influence of Morphological Changes in Amplatzer Device on the Atrial and Aortic Walls Following Transcatheter Closure of Atrial Septal Defects

Objective: This study prospectively investigated morphological changes in Amplatzer Septal Occluder (ASO) over time and the influences of these changes on the atrial and aortic walls after atrial septal defect (ASD) closure.
Methods: Between August 2005 and December 2007, 78 patients with ASD were treated with ASO devices and changes in the device shape, the device thickness, and relations of the discs to the atrial and aortic walls over time were evaluated by transesophageal echocardiography immediately and 3–12 months after deployment.
Results: The maximum unstretched ASD diameter was 16.2 ± 4.8 mm and the device diameter selected was 20.6 ± 5.5 mm. At the time of last follow-up, the device thickness decreased by 17–33%, 6 of 26 devices with a flare shape on the aortic side developed a closed shape, and the relations of the discs to the anterior atrial and aortic walls changed from touching to intermittent compression in 14 of the 78 cases. In these 14 cases, the aortic rim was significantly smaller, the number of flared device shapes on the aortic side/the number of closed shapes immediately after deployment was significantly larger, and the maximum device thickness at the middle part was significantly more decreased than those in other cases.
Conclusion: As the device becomes thinner, loses its flexibility, and often changes from a flare-to-closed shape on the aortic side over time, the edges of ASO can start to compress the atrial and aortic walls. However, erosion was not recognized in these cases.     

Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan

Background:  Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease.
Methods:  We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini-mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated.
Results:  The Revised Hasegawa Dementia Scale and mini-mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials.
Conclusions:  The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer-term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day.     

PHARMACOKINETIC STEREOSELECTIVITY OF TROGLITAZONE,AN ANTIDIABETIC AGENT,IN THE KK MOUSE

Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two asymmetric centres. In the present study, the stereoselectivity of in vitro epimerization in plasma and organ homogenate and in vivo plasma disposition in the KK mouse, an animal model of non-insulin-dependent diabetes, was examined. In the incubation experiments at 37 °C, there was a fivefold to eightfold acceleration of epimerization at the 5 position of the thiazolidine ring in KK mouse plasma compared with that in buffer. However, no inversion at the 2 position of the chroman ring was observed. In addition, there was an approximately 1·3-fold difference in the epimerization rates among stereoisomers at the 2 position of the chroman ring. However, there were no differences in the values of the equilibrium constants of epimerization, and the ratio of epimerization among stereoisomers at the 5 position of thiazolidine ring was almost unity. The acceleration of epimerization is thought to be due to the high degree of protein binding because of the relationship between the initial epimerization rate and the dilution ratio of the plasma. Although acceleration of epimerization was also observed in the 20% homogenates of liver, kidney, and intestine of the KK mouse, the degree of stereoselectivity was lower than in plasma. The analysis of the plasma disposition after intravenous administration of troglitazone stereoisomers, using a kinetic model, indicated that the metabolic clearance in the liver showed a 2·5-fold maximum difference among stereoisomers and that the stereoselectivity of epimerization was low. ©1997 by John Wiley & Sons, Ltd.