Naoki Fujimoto

Lp(a) lipoprotein as a risk factor for coronary heart disease and cerebral infarction

Attempts were made to prepare antisera monospecific for Lp(a) lipoprotein and to investigate the distribution of subjects according to plasma levels of Lp(a) in Japanese controls and patients with coronary heart disease or cerebral infarction. Positive plasma reactions to the double diffusion test for Lp(a) (Ouchterlony) were observed in 32.3% of the healthy Japanese subjects, which is similar to results previously reported in western countries. The plasma threshold level of 17 mg/dl was considered an appropriate point for dividing subjects into positive and negative groups depending on reactions to the double diffusion test. When subjects were divided into two groups at 17 mg/dl, a significant association was found between a high plasma level of Lp(a) and either coronary heart disease or cerebral infarction in the distribution of the cortical artery. These results suggest that Lp(a) may play an important part as a risk factor for coronary heart disease and cerebral infarction.

Regional Cerebral Blood Flow Abnormalities in Nondemented Patients With Memory Impairment

Background. Patients with objective evidence of memory impairment have been considered to be at risk for developing Alzheimers disease (AD). However, little is known about patterns of regional cerebral blood flow abnormalities and their prognostic significance in these patients. Methods. The authors retrospectively studied 28 nondemented subjects with memory loss and investigated patterns of blood flow abnormalities on single photon emission computed tomography (SPECT). Results. The patients were followed up for more than 2 years; during follow‐up, 14 patients (50%) developed AD. The onset of memory impairment in patients who progressed to AD was significantly earlier than in those who remained in a nondemented condition. SPECT data from the initial evaluation were analyzed by region of interest analysis and statistical parametric mapping. Interestingly, both groups of patients shared hypoperfusion in the medial temporal regions and the posterior cingulate. In addition to these regions, significant blood flow reduction in the parietal and anterior cingulate cortices was detected in patients who progressed to AD. Conclusions. These results demonstrate that (1) subjects with an earlier onset of memory loss have an increased risk for developing AD, (2) SPECT can be useful for distinguishing subjects with memory loss who will rapidly progress to AD from those who will not, and (3) perfusion impairment typical of AD was evident even in subjects with memory impairment who remained nondemented.

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

Background and Purpose Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. Case Description We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. Conclusions This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.

High intensity areas on noncontrast T1-weighted MR images in cerebral infarction.

Among 46 noncontrast magnetic resonance studies on patients with cerebral infarction, 11 showed areas of high signal intensity of the involved brain on T1-weighted images. These areas were more frequent in cerebral or cerebellar cortical lesions. Lacunar infarcts in lenticular nuclei, internal capsules, corona radiata, or brain stem did not show any high signal intensity areas on T1-weighted images, whereas the thalamic infarcts did. Sequential studies revealed that these lesions displayed low signal intensity on T2-weighted images at first, and then a high signal intensity area appeared on T1-weighted images. This latter intensity gradually subsided and was replaced by a low intensity area on T2-weighted images. We suggest that these high signal intensity areas on the T1-weighted images in cerebral infarction are caused by hemorrhagic changes at the periphery of the infarction, where blood flow is restored by recanalization or collateral supply.

Lipoprotein abnormalities in survivors of cerebral infarction with a special reference to apolipoproteins and triglyceride-rich lipoproteins

Serum lipid and apolipoprotein concentrations were measured in 37 male survivors of cerebral infarction (CI) and in 30 healthy controls. Both groups had similar total cholesterol levels, but the HDL-cholesterol level was significantly lower and the serum triglyceride level was significantly higher in the CI patients than in the controls. The ApoB level was significantly higher in the CI patients but there was no significant difference between the 2 groups in the levels of the other apolipoproteins (ApoA-I, A-II, C-II, C-III, and E). The HDL-cholesterol/ApoA-I ratio was significantly lower in the CI patients. Both the VLDL-triglyceride and VLDL-cholesterol levels were higher in the CI patients but the VLDL-cholesterol especially its cholesterol ester level was conspicuously high. A population of VLDL particles that bound to heparin on heparin-Sepharose columns was increased in the CI patients. We suggest that cholesterol ester is excessively transferred from HDL to VLDL during the disturbed catabolism of VLDL in CI patients.

Five cases with familial hypercholesterolemia complicated by stroke.

家族性高コレステロール血症 (FH) は生下時より血清総コレステロール (TC) 値が異常に高く, 動脈硬化が早期より進展して高率に虚血性心疾患をおこすが, 脳卒中になることは非常に少ない.FHに脳卒中を合併する場合の特徴を明らかにするために, 自験5症例の脳卒中のタイプ, 各種の危険因子を検討した.2例は皮質枝梗塞であり, そのTC値は400mg/dl以上と高く, HDLコレステロール (HDL-C) 値は30mg/dl以下と低く, 動脈硬化指数は高かった。他の2例は穿通枝梗塞で残り1例は脳内出血であった.これら3例ではTC値が300mg/dl以下, HDL-C値は34~42mg/dlで, 動脈硬化指数は軽度上昇にとどまった.しかし5例に共通した危険因子は高血圧で, これが脳卒中をおこす最も重要な要因と考えられた。高血圧があってもTCとHDL-C値によって動脈病変が異なり, 皮質枝梗塞あるいは穿通枝梗塞になるのであろうと考えられた.

Effects of common carotid artery damage on anti-platelet-aggregability and PGI2 production in rats.

The effects of vascular damage on platelet function were investigated in rats. Common carotid artery specimens 4 mm in length were dissected from male Wistar rats and exposed to ultrasonic treatment or rubbing of the intimal surface. In some cases, carotis was dissected after ligation for 4 hr. The specimens were fixed on a stirring bar and agitated in platelet-rich plasma added with ADP. After determining platelet aggregability, the plasma was subjected to radioimmunoassay for 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha). Anti-platelet-aggregability in the arterial specimens was significantly greater in the sonicated, rubbed or ligated specimens than in the intact group, probably due to the effect of prostacyclin (PGI2). The measurement of 6-K-PGF1 alpha levels yielded similar results. Endogenous arachidonic acid in the vessel wall seems to be utilized in the production of PGI2, which probably acts only on local platelets. The findings indicate the presence of a mechanism that inhibits the formation of platelet thrombi by the accelerated production of PGI2 under conditions favorable for the generation of thrombosis.