Noriaki Matsumura

A CHINESE HERBAL MEDICINE, CHOTO‐SAN, IMPROVES COGNITIVE FUNCTION AND ACTIVITIES OF DAILY LIVING OF PATIENTS WITH DEMENTIA: A DOUBLE‐BLIND, RANDOMIZED, PLACEBO‐CONTROLLED STUDY

CASE REPORT This 81-year-old man presented in January 2004 at the emergency department for a first episode of acute abdominal distension. He had been hospitalized 8 years earlier for a myocardial infarction and atrial fibrillation. He lived at home with his wife. His treatment included aspirin (75 mg/d), an angiotensin-converting enzyme inhibitor, and digoxin. Initial electrolyte analysis showed severe hypokalemia, at 2.0 mmol/L. Natremia, urea nitrogen, and creatinemia were in the normal range. The electrocardiogram showed atrial fibrillation, with a ventricular rate of 92 beats per minute. A plain abdominal ray showed a gaseous distension of the right colon and of the rectum without sigmoid volvulus or fecal impaction. The diagnosis of acute colonic pseudoobstruction was made, and a colonoscopic exsufflation was performed. Kaliuresis was low (18 mmol/L). The patient was given 40 mEq potassium chloride intravenously. Because of the atrial fibrillation, thyroid function tests were performed, which showed latent hyperthyroidism with low thyroid-stimulating hormone (0.015 mUI/mL (normal range 0–15.4)) and normal peripheral hormones (T4, 19.4 pmol/L (normal range 10–25); T3, 5.23 pmol/L (normal range 4.5–9.2)). Clinically, the thyroid was normal. A second exsufflation was performed the day after admission. Kalemia was measured at 2.9 mm/L. The patient was given potassium supplementation orally (20 mEq/d). He was discharged on the tenth day. Kaliemia was 3.9 mmol/L. The abdomen was normal. A beta-blocker was added to his treatment because of the history of myocardial infarction, and potassium supplementation was stopped. The patient was rehospitalized 3 months later, in April 2004, with the same presentation: acute colonic pseudoobstruction and hypokalemia (1.9 mmol/L) with a low kaliuresis (11 mmol/L). Potassium supplementation was given intravenously initially and then orally. Two colonic exsufflations were necessary. The patient was discharged 10 days after admission. Kalemia was measured at 4.9 mmol/L. A third attack of acute colonic pseudoobstruction occurred 1.5 months later, in May 2004. Kalemia was measured at 2.5 mmol/L. The hypothesis of a relationship between hypokalemia and hyperthyroidism was formulated. Thyroid-stimulating hormone was undetectable (0.005 mUI/L (normal range 0.15–4), and free T4 was elevated (33 pmol/L (normal range 10–25)). Treatment with NeoMercazole (40 mg/d) was initiated. Radioactive iodine uptake was 30% at 4 hours, and the patient was treated with 7 milli Curie of 131 Iodine at the beginning of June 2004. Three months later, kalemia remained in the normal range, no colonic pseudoobstruction occurred, and thyroid function had normalized. DISCUSSION This observation of TPP is unusual in two aspects: the age of the patient and the type of paralysis. TPP usually occurs in young Asian men. To our knowledge, it has never been described in an elderly person. The most frequent clinical presentation is recurrent attacks of flaccid weakness, predominantly involving the lower limbs. Bulbar, ocular, cardiac, and respiratory muscles are rarely involved. Smooth-muscle paralysis has never been described. The cardinal biochemical abnormality during an attack is hypokalemia, which is the result of an intracellular shift of potassium, the total body potassium store being normal. The relationship between thyrotoxicosis and hypokalemia is based on the fact that thyroid hormone has been shown to increase sodium/potassium ATPase activity in skeletal muscle, the liver, and the kidneys, resulting in increased intracellular transport of potassium in the setting of hyperthyroidism, but the pathogenic mechanisms of TPP are not totally explained. A defect in the neuromuscular junction, classically suggested, may explain the colonic paralysis observed. As in classical TPP, recurrent attacks of colonic pseudoobstruction occurred until correction of the hyperthyroid status. Hyperthyroidism must be excluded in older people who present with a hypokalemic colonic pseudoobstruction.

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

BackgroundPrevious studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals.MethodsThirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.ResultPercentage decreases from FMD0 to FMD60 were significantly greater in the TM group (−21.19% ± 17.90%; P < 0.001) and the OG group (−17.59% ± 26.64%) than in the control group (6.46% ± 9.17%; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group (−18.91% ± 16.58%) than in the control group (6.78% ± 11.43%; P < 0.001) or the TM group (5.22% ± 37.22%; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = −0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = −0.462; P < 0.05) and the AUC of IRI (r = −0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables.ConclusionDifferences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.

Effects of bile-acid-binding resin (colestimide) on blood glucose and visceral fat in Japanese patients with type 2 diabetes mellitus and hypercholesterolemia: an open-label, randomized, case-control, crossover study.

OBJECTIVE The objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients. METHODS This study was an open-label, randomized, case-control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA(1c)), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level. RESULTS Serum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA(1c) significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 μg/ml to 12.4±9.5 μg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable. CONCLUSIONS Colestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.

Serum uric acid in relation to serum 1,5-anhydroglucitol levels in patients with and without type 2 diabetes mellitus.

OBJECTIVES The aim of this study was to examine the relationship between serum levels of uric acid (UA) and 1,5-anhydroglucitol (1,5-AG) in elderly subjects (60 years or older; mean age, 73.0±7.2 years) with and without type 2 diabetes mellitus (DM). METHODS Subjects with DM (n=97) and without DM (n=360) were recruited from among our outpatients (estimated glomerular filtration rate≥45 mL min⁻¹ 1.73 m⁻², and urine protein equivalent to <1.0 g/L), and a cross-sectional study was performed with simple linear regression and stepwise multiple linear regression analyses. RESULTS The mean serum UA levels of men were significantly higher than those of women in both groups. The mean serum 1,5-AG levels of men were significantly higher than those of women in the non-DM group. There were positive correlations (indicated by Pearsons correlation coefficients) between serum UA levels and 1,5-anhydroglucitol levels in all patients and in both men and women. Simple linear regression and multiple linear regression analyses showed that the serum 1,5-AG levels were significantly and positively correlated with the serum UA level in both the non-DM group and the DM group. In the non-DM group, HbA1c levels, as well as 1,5-AG levels, were positively correlated with serum UA levels. Furthermore, the correlation between 1,5-AG and UA levels was stronger in subjects with DM than in subjects without DM. CONCLUSIONS These results suggest that the serum 1,5-AG level is an independent factor associated with serum UA levels in the nondiabetic state, as in DM.

Four-year prospective study of the influence of elevated serum lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type-2 diabetes

Background:  The purpose of the present paper was to elucidate the influence of an elevated serum lipoprotein (a) (Lp(a)) concentration on the incidence of ischemic heart disease (IHD) and perforating artery occlusion‐type cerebral infarction (CI) in elderly patients with type‐2 diabetes.

Association Between Pulse Wave Velocity and a Marker of Renal Tubular Damage (N-Acetyl-β-D-Glucosaminidase) in Patients Without Diabetes

The authors assessed the association between the ratio of urinary activity of N‐acetyl‐β‐D‐glucosaminidase (NAG) to creatinine and the brachial‐ankle pulse wave velocity (baPWV) in patients without overt diabetes mellitus (DM). This was a cross‐sectional study of 233 patients who had an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and no history of kidney disease. Patients were divided into two groups: high NAG group (>5.8 U/g creatinine) and low NAG group (≤5.8 U/g creatinine). Mean baPWVs of the high NAG group were significantly higher than those of the low NAG group in both the eGFR ≥30 and <60 tertiles and the eGFR ≥60 and <90 tertiles. The baPWV was positively correlated with NAG in all patients (r=0.341, P<.001). Stepwise multivariate regression analysis showed that the baPWV was significantly related with NAG, age, and systolic blood pressure. Elevated NAG is related to elevated arterial stiffness in patients without DM.

Creutzfeldt–Jakob disease with V180I mutation and senile plaque

Alzheimer’s disease (AD) and Creutzfeldt–Jakob disease (CJD) are both characterized by the accumulation in the brain of abnormally folded proteins, a process leading to neurodegeneration. In AD, amyloid-b (Abeta) peptide aggregates in extracellular formations known as senile plaques, while in CJD a protease-resistant prion protein (PrP) accumulates in neurons and extracellular amyloid-like aggregates. Co-localizations in the same neuropathological structures of both proteins have been reported in patients affected by CJD, raising speculation about a possible pathogenic overlap between AD and CJD. Although codon 129 polymorphism of the prion protein gene (PRNP) represents a major genetic risk factor for CJD, there has been a growing interest both in the role of PRNP 129 polymorphism in the elderly and in the neurodegenerative processes, including AD. A recent meta-analysis in white patients also revealed that PRNP 129 is associated with a significantly higher risk of AD. In contrast to these studies, other studies could not find any association between this polymorphism and AD. Similar results have been reported in AD subjects of non-white ethnicity in Japan and South Korea. These contradictory results may be due to the different sizes of the population analyzed or to the differences in the distribution of PRNP genotypes between different ethnic groups. Other possible explanations include lack of examination of senile plaque in autopsy findings and premature death prior to the development of AD lesions. We encountered a 79-year-old Japanese man with CJD with the causative point mutation of valine to isoleucine at codon 180 (CJD V180I). His polymorphic codons showed methionine/valine heterozygosity at codon 129 and glutamine homozygosity at codon 219. His status progressed rapidly to akinetic mutism, and he died of a lung abscess 12 months after the symptoms of dementia appeared. In magnetic resonance imaging (MRI) of the brain, the cerebral cortex was depicted as high-intensity lesion by T2-weighted, diffusionweighted (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging, except a portion of the right parietal lobe and both temporal lobes. These MRI findings were highly suggestive of CJD and led us to a premortem diagnosis. Although the abnormal lesions of sporadic CJD (sCJD) seen in MRI are varied, those of CJD V180I are rather uniform. There were no visual or cerebellar symptoms in the early stage, and the medial occipital and cerebellar cortices were not involved until the terminal stage. The high-intensity area was depicted along the cortical ribbon by DWI, but not in the optical area of the occipital lobe or cerebellum in the present case. At autopsy, the brain weighed 1180 g. Macroscopically, mild cerebral atrophy was present and the cerebral cortex was clearly thinned in coronal sections. Histopathologically, the cerebral cortex showed severe spongiform change, and neuronal atrophy and loss. However, neurons were relatively preserved compared with those of typical sCJD. Both cerebral cortex and white matter showed gliosis, which tended to be weak in the severest spot of spongiform change. Immunohistochemical staining with anti-PrP monoclonal antibody 3F4 showed a moderate synaptic type of diffuse deposition in the cerebral cortex (Fig. 1). Using an Abeta stain, many senile plaques (Braak stage II) were found extensively, together with spongiform changes and amyloid angiopathy in the cerebral cortex (Fig. 2). There were only a few neurofibrillary tangles. There was no CJD pathology in the cerebellum. Point mutations in the PRNP gene vary significantly in frequency between countries. A V180I mutation is extremely rare in European and North American countries, but it is more common in Japan than anywhere else, where it is restricted to a solely Japanese population. Jin et al. clarified the clinical characteristics of 9 Japanese CJD V180I patients by comparing Geriatr Gerontol Int 2009; 9: 210–212

Asymptomatic leukocyturia and the autonomic nervous system in women

Background:  The present study sought to investigate the relationship between asymptomatic leukocyturia (ASL) and autonomic nervous function by power spectral analysis of the R‐R intervals in women.

Repeated episodes of paralytic ileus in an elderly diabetic patient treated with voglibose.

tality from hemorrhage in lumbar puncture under low-dose aspirin treatment than from the increased risk of cardiovascular or cerebrovascular incidence due to discontinuation. The clinical decision about whether to discontinue aspirin for elective lumbar puncture is of high clinical importance because of the high number of patients treated with low-dose aspirin who undergo elective lumbar puncture for early dementia diagnosis. A discontinuation of aspirin for dementia diagnostics should be regarded skeptically especially in patients showing signs of vascular lesions on brain imaging. Controlled prospective studies are necessary to answer this important clinical question.

Asymptomatic Pyuria in Diabetic Women

The aim of the present study was to determine the prevalence of and the host factors for asymptomatic pyuria (ASP) in women with type 2 diabetes. The study included 179 type 2 diabetic women and consecutive 455 non-diabetic women attending as out-patients in 1996. Patients with symptoms of a urinary tract infection were excluded. ASP was defined as the presence of more than 10 leukocytes/high-power field in a random urine sample. Diabetic women more often had ASP than non-diabetic women (27.9 vs. 15.8%, P<0.001). The prevalence of ASP was significantly increased in patients with a duration of diabetes exceeding 15 years (0 approximately 4 years; 20.3%, 5 approximately 9 years; 24.3%, 10 approximately 14 years; 23.8%, and > or =15 years; 46.3%). No differences were evident in HbA(1C) between diabetic patients without ASP and those with ASP. Diabetic women with ASP more often had diabetic retinopathy, neuropathy, nephropathy, cerebrovascular disease, ischemic heart disease, and hyperlipidemia than those without ASP. However, no statistically significant differences were evident in the prevalence of hypertension, constipation, or dementia. As the degree of neuropathy increases, it is accompanied by an increasing prevalence of ASP (none, 21.4%; blunt tendon reflexes, 24.5%; symptomatic, 50.0%; and gangrene, 66.6%). The prevalence of ASP was significantly increased in the patients with proliferative diabetic retinopathy (none, 23.2%; background, 29.4%; pre-proliferative, 18.2%; and proliferative, 50.0%). As the degree of nephropathy increases, it is accompanied by an increasing prevalence of ASP (none, 20.0%; microalbuminuria, 31.9%; macroalbuminuria, 37.0%; and renal failure, 60.0%). Thus, the prevalence of ASP is increased in women with diabetes and increased with longer duration of diabetes but was not affected by glucose control. The incidence of ASP increases significantly as diabetic microangiopathy becomes severer.