Biomedical subjects

Makoto Higuchi

Publications and source records attributed to Makoto Higuchi.

42 records · Page 3Linked to original sources

PubMed2002

Neuroanatomical correlates of low body weight in Alzheimer's disease: a PET study.

Weight loss is a common problem in patients with Alzheimer's disease (AD) and this might be associated with an increased risk for mortality. Recent evidences have suggested that certain brain dysfunctions may result in impaired nutritional status in AD patients. However, the mechanism of body weight loss in AD remains enigmatic. To investigate a possible association between low body weight and regional brain dysfunction, the authors conducted the correlational analysis of body mass index (BMI) with regional brain glucose metabolism using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Twenty-seven patients with probable AD were divided into two groups: the low BMI group and the normal BMI group. Regional brain glucose metabolic ratios were calculated using the cerebellar hemisphere as a reference region. Comparisons were made of regional brain metabolic ratios between the low BMI group and the normal BMI group. Correlations of the glucose metabolic ratio with BMI were also assessed in all patients with AD. In the comparison between the two groups, glucose metabolic ratio in the anterior cingulate cortex (ACC) was significantly lower in the low BMI group, whereas no significant differences were found in all the other brain regions. Furthermore, regional glucose metabolism in the ACC had a significant and positive correlation with BMI (r=.450, P=.018). After adjustment for age, gender and disease duration, regional glucose metabolism in the ACC was independently associated with BMI. Our findings suggest that the ACC may be preferentially involved in the regulation of nutritional status in AD patients, and provides a new insight into developing strategies for prevention and treatment of undernutritional demented patients.

Age Factors↗

PubMed2002

Differential cognitive effects of ebastine and (+)-chlorpheniramine in healthy subjects: correlation between cognitive impairment and plasma drug concentration.

AIMS: It has been widely recognized that classical antihistamines induce sedation as an adverse effect, while second-generation antihistamines have few if any sedative effects. In order to evaluate the sedative properties of ebastine, a second-generation antihistamine, its effect on cognitive performance in healthy subjects was compared with placebo and (+)-chlorpheniramine. METHODS: Twelve healthy male subjects were instructed to perform six types of attention-demanding cognitive tasks, and objective measurements of reaction times and accuracy was made before and after drug administration. Their sleepiness levels were also monitored. Test drugs were ebastine 10 mg, placebo and two doses of (+)-chlorpheniramine 2 mg and 6 mg, as positive controls. Plasma drug concentrations at the end of the study were analysed. RESULTS: After treatments with (+)-chlorpheniramine, the reaction times of the tasks were significantly prolonged (e.g. ratios of after/before dosing: placebo (0.998 +/- 0.113) vs (+)-chlorpheniramine 2 mg (1.103 +/- 0.083; P<0.05) or (+)-chlorpheniramine 6 mg (1.170 +/- 0.139; P<0.001) in a 7 ms visual discrimination time task) and the accuracy was significantly decreased (e.g. ratios: placebo (1.038 +/- 0.158) vs (+)-chlorpheniramine 2 mg (0.792 +/- 0.202; P<0.01) or (+)-chlorpheniramine 6 mg (0.837 +/- 0.222; P<0.05) in a 7 ms task). On the other hand, performance was not affected by ebastine or placebo treatment (e.g. ebastine 10 mg (reaction time ratio; 1.014 +/- 0.067 and accuracy ratio; 0.990 +/- 0.146) in a 7 ms task). Subjective sleepiness was also not affected by ebastine but (+)-chlorpheniramine significantly increased sedation. With respect to the relationship between plasma drug concentrations and task performance, the latter deteriorated with an increase in plasma (+)-chlorpheniramine concentration (e.g. r=0.439 (P=0.007) in a 5 ms and r = 0.352 (P=0.039) in a 7 ms task), but it did not correlate with the plasma concentration of carebastine, an active metabolite of ebastine. CONCLUSIONS: Ebastine 10 mg did not cause any cognitive impairment or subjective sleepiness. On the other hand, (+)-chlorpheniramine impaired cognitive function and induced sleepiness even at 2 mg, the recommended dose in over-the-counter medication. In addition, impaired CNS performance was significantly correlated with plasma (+)-chlorpheniramine concentration.

Administration, Oral↗

PubMed2002

A case of nephrotic syndrome due to lupus nephritis which was controlled with low-density lipoprotein apheresis.

Our report discusses a 29 year old female patient with nephrotic syndrome due to lupus nephritis, biopsy-proven World Health Organization classification Types IVb and V that was controlled with low-density lipoprotein (LDL) apheresis. She was initially treated with steroid therapy, including methylprednisolone pulse therapy, and the serological activity of her systemic lupus erythematosus was suppressed. However, her nephrotic state, accompanied by severe hyperlipidemia, persisted despite the steroid therapy. Since we could not obtain her consent to administer immunosuppressants such as cyclophosphamide, we tried to treat her using LDL apheresis (LDL-A). We found that her urine protein excretion, hyperlipidemia, hypoalbuminemia, and renal function improved following the initiation of LDL-A. This suggests that LDL-A may be an effective therapy for nephrotic syndrome due to lupus nephritis through short-term amelioration of hyperlipidemia.

Adult↗

PubMed2002

Combined Analysis of CSF Tau Levels and [(123)I]Iodoamphetamine SPECT in Mild Cognitive Impairment: Implications for a Novel Predictor of Alzheimer's Disease.

OBJECTIVE: The aim of this study was to establish an objective and reliable index to predict the development of Alzheimer's disease in a large pool of elderly patients with mild cognitive impairment. METHOD: Twenty-three patients with probable Alzheimer's disease, 22 patients with mild cognitive impairment who eventually developed Alzheimer's disease, eight patients with mild cognitive impairment who did not develop dementia, and 19 cognitively normal subjects were included in the study. The authors constructed a new diagnostic index, the CSF-CBF index, based on CSF tau levels divided by regional cerebral blood flow (CBF) in the posterior cingulate cortex. RESULTS: Receiver operating characteristic analysis showed that applying a cutoff value for the CSF-CBF index of 296.0 achieved a sensitivity of 88.5% and a specificity of 90.0% in discriminating mild cognitive impairment that progressed to Alzheimer's disease from mild cognitive impairment that did not progress to Alzheimer's disease. CONCLUSIONS: The CSF-CBF index is useful in predicting Alzheimer's disease in subjects with mild cognitive impairment.

Aged↗

PubMed2002

Tau and axonopathy in neurodegenerative disorders.

The microtubule (MT)-associated protein (MAP) tau in neurons has been implicated as a significant factor in the axonal growth, development of neuronal polarity, and the maintenance of MT dynamics. Tau is localized to the axon, and is known to promote MT assembly and to stabilize axonal MTs. These functions of tau are primarily regulated by the activities of protein kinases and phosphatases. In Alzheimer's disease and other neurodegenerative disorders, abundant filamentous tau inclusions are found to be major neuropathological characteristics of these diseases. Both somato-dendritic and axonal tau lesions appear to be closely associated with axonal disruption. Furthermore, recent discoveries of pathogenic mutations on the tau gene suggest that abnormalities of tau alone are causative of neurodegeneration. Finally, analyses of transgenic mice that express human tau proteins have enabled in vivo quantitative assessments of axonal functions and have provided information about mechanistic relationships between pathological alteration of tau and axonal degeneration.

Animals↗

PubMed2002

Epidemiology and clinical aspects on hepatitis C.

Hepatitis C virus (HCV) infects an estimated 170 million persons worldwide, and 2 million persons in Japan. HCV is a major cause of chronic liver diseases, especially hepatocarcinogenesis, and the number of patients with HCV-related hepatocellular carcinoma (HCC) is increasing worldwide as well as in Japan. Most patients with acute hepatitis C develop chronic hepatitis. Spontaneous disappearance of HCV in patients with type C chronic liver disease is uncommon, and it tends to progress to further advanced and more severe liver disease, ultimately to HCC over a period of 30 years in most cases. Chronic liver disease due to HCV infection is commonly associated with extrahepatic manifestation, for example cryoglobulinemia. Antiviral treatment for HCV infection with interferon alone during 24 weeks was associated with a low rate (less than 10%) of sustained virologic response (SVR), especially in patients infected with HCV genotype 1b and high HCV RNA concentration. However, combination therapy of interferon and ribavirin raises the SVR rate. More recently, pegylated interferon used for treatment of chronic hepatitis C resulted in a high SVR rate. These modalities of antiviral treatment will reduce HCC occurrence. So far, there is no HCV vaccine in spite of many efforts.

Acute Disease↗