Potential hippocampal region atrophy in diabetes mellitus type 2: a voxel-based morphometry VSRAD study

Purpose

Among diabetes mellitus type 2 (DM2) patients, the frequency of cognitive dysfunction is higher and the relative risk of Alzheimer’s disease (AD) is approximately twice that of nondiabetics. Cognitive impairment symptoms of AD are induced by limbic system dysfunction, and an early-stage AD brain without dementia has the potential for atrophy in the hippocampal region. In this study, we estimated potential hippocampal region atrophy in DM2 and pursued the association between DM2 and cognitive impairment/AD.

Materials and methods

Voxel-based morphometry analysis was performed in 28 diabetics (14 men, 14 women; ages 59–79 years, mean 70.7 years) and 28 sex- and agematched (±1 year) nondiabetics. Severity of gray matter loss in the hippocampal region and whole brain were investigated. Group analysis was performed using twotailed unpaired t-test; significance was assumed with less than 1% (P < 0.01) of the critical rate.

Results

There was a significant difference between diabetics and nondiabetics regarding the severity of hippocampal region atrophy and whole-brain atrophy. Only diabetics showed a positive correlation for severity of hippocampal region atrophy and whole-brain atrophy (rs = 0.69, P < 0.0001).

Conclusion

Aged DM2 patients have the potential for hippocampal region atrophy, and its dysfunction can be related to the expression of a cognitive impairment that resembles AD.     

Enhanced regional washout of technetium-99m-sestamibi in patients with coronary spastic angina

BACKGROUND: Reverse redistribution and rapid washout of 99mTc-sestamibi are observed in patients with acute myocardial infarction and may indicate viable myocardium. However, the clinical significance of this phenomenon has not been rigorously examined in other cardiac diseases. Thus, we investigated whether reverse redistribution and washout of 99mTc-sestamibi could be used in the diagnosis and follow-up of patients with coronary spastic angina. METHODS: Thirty patients diagnosed as coronary spastic angina were examined. During coronary arteriography, spasm was induced by provocation test with ergonovine, and only total or subtotal occlusion was considered positive. Myocardial perfusion tomography was obtained 45 min (early) and 3 hr (delayed) after 99mTc-sestamibi injection. Segmental defect score was visually graded from 0 (normal) to 4 (defect), and a total defect score was determined as the sum of defect scores for all segments. Washout rate of 99mTc-sestamibi from the myocardium was calculated for each segment. After medical treatment with calcium antagonists and nitrates for 3 months, 99mTc-sestamibi imaging was repeated. RESULTS: Out of 30 patients, on the early images 17 (57%) patients demonstrated decreased 99mTc-sestamibi uptake in spastic segments; on the other hand, 24 (80%) patients did decreased 99mTc-sestamibi uptake in spastic segments on delayed images. Total defect scores in delayed images were higher than those in early images (6.9 +/- 0.3 vs. 3.6 +/- 0.4, p < 0.01). Reverse redistribution of 99mTc-sestamibi was observed in 17 out of 30 patients (57%) with coronary spastic angina. Washout rate of 99mTc-sestamibi from spastic segments was higher than that from non-spastic segments (16 +/- 2% vs. 11 +/- 5%, p < 0.01). After medical treatment, washout rate from spastic segments was decreased to 10 +/- 4 (p < 0.01), and left ventricular ejection fraction was increased from 63 +/- 8% to 73 +/- 4% (p < 0.01). CONCLUSION: Rapid washout of 99mTc-sestamibi was observed in patients with coronary spastic angina and might indicate that the ability of myocyte to retain the tracer was impaired due to repetitive brief ischemia by coronary spasm. The early and delayed 99mTc-sestamibi imaging provides useful information for the diagnosis and responses to the treatment in patients with coronary spastic angina.     

Structural determination of a new mutagenic heterocydic amine, 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMeIgQx), present in beef extract

We previously found two new mutagens, compounds I and II, inbacteriological-grade beef extract by monitoring the mutagenicityto a new Salmonella strain, YG1024; compound I was identifiedas 2-amino-4-hydroxymethyl-3,8-dimethyli-midazo[4,5-f]quinoxaline(4-CH₂OH-8-MeIQX) In the present study, we isolated compoundII from the beef extract, which accounted for 2% of the totalmutagenicity of materials adsorbed on blue cotton. Further,we found that a large quantity of compound II was produced byheating a mixture of creatine, threonine and glucose (1:1:0.5)at 200^°C for 5 h, the level being 860-fold of that in thebeef extract. The structure of this compound was determinedto be 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMeIgQx)by X-ray crystallography. The amount of 7,9-DiMeIgQx in bacteriological-gradebeef extract was estimated to be 53 ng/g. This compound induced13 800 and 670 revertants of S.typhimurium YG1024 and TA98 respectively,per µg in the presence of S9 mix.     

Different effects of oral administration of synthetic trypsin inhibitor on the pancreas between cholecystokinin-A receptor gene knockout mice and wild type mice

The synthetic trypsin inhibitor camostat has been used for the treatment of acute and chronic pancreatitis in Japan based on the evidences obtained from a rat experimental model. However, rats differ from other rodents and from humans in terms of lacking a gallbladder and no response of pancreatic bicarbonate secretion to cholecystokinin (CCK). In the present study, we determined whether oral administration of camostat showed a trophic effect in mice as observed in rats and whether the trophic effect, if substantial, was mediated via the CCK-A receptor, using CCK-A receptor gene targeting mice. The chow containing 0.1% camostat was fed to 8-month-old mice. Three- and seven-day treatments with camostat did not affect pancreatic wet weight in CCK-A receptor (+/-) mice. After 14-day treatment, the ratio of pancreatic wet weight/body weight was significantly lower in CCK-A receptor (-/-) than (+/+) mice. The protein and chymotrypsin contents were lower and amylase content was higher in CCK-A receptor (-/-) mice, compared to (+/+) mice. No pathological findings were observed by histological examination. Camostat has a trophic effect on the pancreas in mice and this effect is mediated via the CCK-A receptor, but is less potent than in rats.     

The initial fixation of the press-fit acetabular shell – clinical observation and experimental study

The initial solid fixation of an uncemented acetabular component affects the amount of bone ingrowth. We had several problems with broken screws in cases of acetabular revision. In recent years, the development of uncemented components without screws has attempted to improve these problems. We started to use “press-fit”-type acetabular shells in November 1996. Our thirty cases undergoing 2 mm under-reaming show good initial stability. The aim of our biomechanical study was to assess the most suitable degree of under-reaming of the bony acetabulum for the implantation of an uncemented hemispherical porous coated component. Received: 15 January 1999     

Central acinic cell carcinoma of the mandible: Report of a case

Central acinic cell carcinoma is extremely rare; only six cases have been reported in the literature. An unusual case of central acinic cell carcinoma of the mandible in an 84-year-old Japanese woman is presented. This is thought to be the seventh case of central acinic cell carcinoma described in the English literature.     

Local recurrence of pancreatic cancer successfully treated with gemcitabine

We report a patient for whom systemic chemotherapy using gemcitabine was effective against local recurrence of pancreatic cancer. A 58-year-old man underwent pancreatoduodenectomy for a pancreatic head cancer. The diagnosis was Stage IVb poorly-differentiated tubular adenocarcinoma, scirrhous type, pT4, PL (+), P0, H0, pN2. However, after 21 months, gastrointestinal bleeding occurred. Gastroscopy and CT examination revealed a mass at the cut-end of the pancreas invading the stomach. The serum CA19-9 level was found to be elevated. Systemic chemotherapy was performed with a regimen of gemcitabine 1,000 mg/m2/week for 2 weeks, followed by a week rest. The recurrent tumor in the stomach disappeared, and the mass at the cut-end of the pancreas became small. The serum CA 19-9 level regained the normal value. Two years after the diagnosis of recurrence, he returned to work, and his chemotherapy is being continued as an outpatient.     

Case report: a young woman with advanced esophageal cancer showing pathological complete response to neoadjuvant chemotherapy (CDDP, 5-FU and ADM)

A 32-year-old woman was admitted to our hospital with dysphagia. An upper gastrointestinal series revealed Borrmann type 2 esophageal cancer in the lower thoracic esophagus. Because direct invasion of the thoracic aorta was suspected, FAP therapy (CDDP, 5-FU and ADM) was given as neoadjuvant chemotherapy. After completion of two courses, her dysphagia resolved and the tumor shrank by over 90%, so radical surgery was performed. No lesions were found when the resected specimen was examined macroscopically. The only histological change was hyperplasia of collagen fibers in the submucosa, lamina propria and adventitia of the esophagus. No cancer cells and no metastases to the lymph nodes were observed. Because the tumor had completely disappeared, the histological effect of chemotherapy was classified as grade 3, i.e., pathological complete response (PCR). The response to FAP therapy was excellent and no serious adverse events occurred. Therefore, this is one of the treatments that should be actively applied in patients who have advanced esophageal cancer with suspected lymph node metastasis and invasion of other organs.     

Non-specific hyperamylasemia in shosin beri-beri

Several reports demonstrate non-specific hyperamylasemia in cardiac surgery or diabetic ketoacidosis. We report here for the first time non-specific hyperamylasemia in a cardiovascular beri-beri case who showed shock with severe metabolic acidosis. Her echocardiography revealed hyperkinetic wall motion of the small left ventricle. Despite intravascular volume expansion in parallel with dopamine administration, her blood pressure did not recover. Abdominal computed tomography (CT) did not reveal pancreatic swelling or any other signs of acute pancreatitis. Her history suggested a possibility of cardiovascular beri-beri due to chronic alcoholism. Thiamine administration dramatically reversed her haemodynamic derangements, metabolic acidosis and even relieved her abdominal pain. Isozyme examinations for hyperamylasemia showed that most of the serum amylase consisted of salivary type. This case report expands our information on non-specific hyperamylasemia encountered in the emergency setting.     

Sporadic cerebral amyloid angiopathy presenting with dementia and prominent capillary beta-amyloid deposition: a case report]

We report a sporadic case of unusual cerebral amyloid angiopathy (CAA) with prominent capillary involvement. A 67-year-old doctor developed gait disturbance, resting tremor and rigidity. He was diagnosed to have Parkinson's disease, for which the treatment with levodopa was effective. Four years later he began to exhibit progressive cognitive decline and behavioral abnormalities consisting of hallucination and agitation. Subsequently, his condition steadily worsened and became bedridden with severe dementia, and he died eight years after the disease onset. During the clinical course, there had been no episode of stroke. Postmortem examinations revealed the typical pathology of Parkinson's disease with frequent cortical Lewy bodies in the amygdala. The most striking pathological feature of this patient was widespread CAA where prominent beta-amyloid (A beta) deposition was observed in the capillaries of the neocortex, most pronouncedly in the occipital lobe, as well as leptomeningeal and cerebral medium-sized and small vessels. Further, perivascular plaques were found in half of the amyloid-laden capillaries. Tau-positive dystrophic neurites were only sparsely detectable within a few perivascular plaques. Despite the severe A beta pathology, there was no microaneurysmal dilatation, fibrinoid necrosis or vascular occlusion. There was only one small ischemic lesion in the brain. The cerebral white matter was unremarkable. Senile plaques of neuritic type and neurofibrillary tangles were mostly limited to the hippocampal regions and, to a lesser degree, in the amygdaloid nucleus, which did not meet the neuropathological criteria of Alzheimer's disease. On the gene analyses, his apolipoprotein E (ApoE) genotyping was verified to be heterozygous epsilon 3/epsilon 4, and no mutation was seen in exons 16 and 17 of the amyloid precursor protein gene. Severe A beta capillary angiopathy as seen in our patient is exceptional in sporadic CAA. Further, A beta angiopathy of this patient was notable in the absence of an associated cerebrovascular disease despite prominent A beta deposition in the vessel walls. Regarding the development of his severe dementia, the limbic pathology of Lewy body disease might be one of the potential causes, but A beta angiopathy appears more likely because of its severity. We speculate that widespread A beta deposition disregulates the blood-brain barrier of the capillaries leading to a disturbance of the microcirculation throughout the cerebral cortex without obvious ischemic disintegration of the neuropil. We should take into consideration that A beta angiopathy can present as progressive dementia without cerebrovascular disease.