A case of ischemic stroke associated with protein-losing gastroenteropathy and protein S deficiency.

Protein-losing gastroenteropathies are characterized by an excessive loss of serum proteins into the gastrointestinal tract, resulting in hypoalbuminemia. Some rare cases are complicated with ischemic stroke. We report a 24-year-old woman who developed acute dysarthria and right hemiplegia 4 months after delivering her first baby by cesarean section. Diffusion-weighted magnetic resonance imaging showed a high-intensity signal in the left anterior cerebral artery territory and middle cerebral artery territory. She had marked hypoalbuminemia and decreased protein S activity. We identified protein-losing gastroenteropathy as the cause of the hypoalbuminemia, and she had a missense mutation of the PROS 1 gene, which was associated with decreased protein S activity. We speculated that the development of protein-losing gastroenteropathy accelerated the decline in protein S activity and caused cerebral infarction.

[Aseptic meningitis as paraneoplastic syndrome related to chronic myeloid leukemia in chronic phase].

Chronic myeloid leukemia (CML) is a clonal hemopoietic stem cell disorder characterized by reciprocal translocation between the long arms of chromosomes 9 and 22 that produces the fusion BCR-ABL1 gene. Major manifestations in CML patients are increased white cell count and splenomegaly. In this case, the patient presented with aseptic meningitis and showed symptoms, such as disorientation, double vision, and neurogenic bladder disorder. Pulse steroid and antibiotic treatment was ineffective for these symptoms; however, the combination therapy with these drugs and dasatinib was very effective. Moreover, our patient had myelopathy that could have been induced by dasatinib after the treatment was started. To our knowledge, this is the first report of meningitis of the paraneoplastic syndrome associated with CML.

Clinical comorbidities correlated with a response to the cerebrospinal fluid tap test in idiopathic normal-pressure hydrocephalus.

AIMS: The mainstay of treatment for idiopathic normal-pressure hydrocephalus (iNPH) is spinal fluid shunting. A tap test (TT) is recommended as an indication of shunting. Patients with iNPH are often elderly and have multiple comorbidities affecting the shunting outcome. We investigated the factors affecting TT in patients with iNPH. METHODS: Seventy-five patients with iNPH were admitted to our department for a TT from April 2010 to May 2021. The patients were divided into a responsive group and an unresponsive group according to the clinical outcomes after TT on the Timed Up and Go Test (TUG), Mini-Mental State Examination (MMSE), or iNPH grading scale. Factors affecting the TT were compared between the responders and nonresponders. RESULTS: There were 38 patients (50.7%) in the TT responder group, and the prevalence of improvement was 82.9% in the TUG, 27.6% in the MMSE, and 76.3% in the iNPH grading scale. There were no significant differences in the vascular risk factors between the two groups. The prevalence of lumbar spondylosis, compression fracture, severe periventricular hyperintensity, deep and subcortical white matter hyperintensity (DSWMH), and old cerebral infarcts was significantly higher among the TT nonresponders. The logistic regression analysis showed that severe DSWMH and lumbar spondylosis were associated with a TT nonresponse (p < 0.001 and p = 0.003, respectively). Shunting was performed in 22 patients, 19 of whom were TT responders. CONCLUSION: Severe DSWMH and lumbar spondylosis were associated with a poor response to the TT in iNPH patients. We should consider risk factors when selecting candidates for shunt surgery.

The effects of losartan on signal-averaged P wave in patients with atrial fibrillation.

BACKGROUND: Losartan has recently been reported to suppress atrial structural remodeling. However, few reports exist on signal-averaged electrocardiography (ECG) for preventing atrial electrical remodeling. We examined the effect of losartan on atrial electricity by using signal-averaged ECG of P waves. METHODS: The subjects comprised 40 patients with essential hypertension complicated with symptomatic paroxysmal atrial fibrillation. The patients received pilsicainide for the complication; they were defibrillated and divided into two subgroups for antihypertensive therapy: calcium antagonist-administrated (CB) and losartan-administrated (LOS) groups. We recorded the signal-averaged electrocardiography of P waves and calculated (1) filtered P wave duration (PD), (2) the voltage integral for the entire P wave (integral-p), and (3) the root mean square voltages of the terminal 40, 30, and 20 ms (RMS-40, RMS-30, and RMS-20). Procollagen C propeptide type I (PIP) and A- and B-type natriuretic peptide (ANP and BNP, respectively) levels in the groups were measured before and after antihypertensive agent administration. RESULTS: RMS-20 increased significantly and PD decreased significantly in the LOS group 24 weeks after antihypertensive drug administration; however, they remained unchanged in the CB group. Integral-p decreased significantly in both groups, and the decrease rate was significantly higher in the LOS group. Serum BNP levels decreased significantly only in the LOS group. CONCLUSIONS: Losartan inhibits atrial remodeling by inhibiting left atrial fibrosis as indicated by the procollagen C propeptide type I, ANP, and BNP levels. Signal-averaged ECG demonstrated that losartan suppresses atrial fibrillation recurrence by improving atrial conduction disturbance.

The effect of G-CSF in a myocardial ischemia reperfusion model rat.

PURPOSE: It has been reported that G-CSF administration improves cardiac function by reducing the area of the infarct in a myocardial infarction model rat. In the present study, myocardial infarction model rats, produced by ligation of the left anterior coronary artery, were prepared. The G-CSF effect for treating cardiac muscle cell disorders by ischemia reperfusion was studied. METHODS: Myocardial infarction model rats were produced by ligation of the left anterior descending coronary artery in 12-week-old Wistar rats. G-CSF was administered subcutaneously daily at a dose of 100 microg/kg/day for 5 days to rats with a complete ligation (MI-G group, n=6) and rats in which the ligated coronary artery was reperfused 30 minutes after the ligation (R-G group, n=6). Physiological saline was subcutaneously administered to rats with a complete ligation and reperfusion (MI-C and R-C groups, respectively, n=6 each), as controls. After 4 weeks, the infarct area ratio (%), cardiac function on echocardiography (left ventricular ejection fraction), and a myocardial histopathological diagnosis were carried out and the results compared among the groups. RESULTS: No significant differences were found in the proportion of the residual heart muscle in the infarct lesion, myocardial wall thickness, or left ventricular ejection fraction between the MI-G and MI-C groups. In contrast, the infarct area, myocardial wall thickness, and left ventricular ejection fraction were significantly improved in the R-G group compared to the R-C group (p<0.05). CONCLUSIONS: Any inhibitory effect of G-CSF on the infarct lesion was found in the myocardial infarction reperfusion model rat, but only a small effect was found in rats with a complete ligation-induced myocardial infarction. The findings in the present study, therefore, suggest that G-CSF is effective for treating cardiac muscle cell disorders by ischemia reperfusion.

Clinical study with azelnidipine in patients with essential hypertension. Antiarteriosclerotic and cardiac hypertrophy-inhibitory effects and influence on autonomic nervous activity.

A dihydropyridine calcium (Ca) antagonist, azelnidipine (CAS 123524-52-7, Calblock), exhibits hypotensive effects for a prolonged duration, and has been reported to have a strong antiarteriosclerotic action due to its high affinity for vascular tissues and antioxidative action. It has also been reported that azelnidipine does not cause tachycardia associated with the baroreceptor reflex due to vasodilatation. In this study, the antiarteriosclerotic and cardiac hypertrophy-inhibitory effects, and the autonomic nervous activity in essential hypertension of azelnidipine were investigated. The study was performed using the following 2 protocols: 1) Pulse wave velocity (PWV), carotid arterial intima media thickness (IMT), echocardiography, high sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), adiponectin, brain natriuretic peptide (BNP), and 8-isoprostane were measured after an initial treatment with azelnidipine. 2) The treatment was switched to azelnidipine in patients who had previously been under treatment with amlodipine for essential hypertension, and 123I-metaiodobenzylguanidine myocardial scintigraphy (123I-MIBG), measurements of plasma norepinephrine, atrial natriuretic peptide (ANP), and BNP, Holter electrocardiography, and heart rate variability analysis were performed. PWV, IMT, hs-CRP, IL-6, and TNF-alpha significantly decreased. The levels of 8-isoprostane, an antioxidative marker, were also significantly decreased, while adioponectin levels were significantly increased after the initial treatment with azelnidipine. After switching from amlodipine, azelnidipine exhibited a hypotensive effects comparable to amlodipine, and significantly decreased heart rate and the total number of extrasystoles. Noradrenaline levels and the LF/HF ratio were significantly decreased, and the washout rate was significantly reduced on 123I-MIBG myocardial scintigraphy. These findings suggest that azelnidipine inhibits the enhancement of sympathetic nervous activity and the progression of arteriosclerosis through its antioxidative effects.

Risk factors associated with soft coronary artery plaques in Japanese, as determined by 16 slice multidetector-row computed tomography.

PURPOSE: The acute coronary syndrome is often caused by the rupture of plaques and thrombus formation even without significant stenosis, and patients with soft plaques, but without significant stenosis evidenced by coronary angiography (CAG), often develop an acute coronary syndrome. To address this discrepancy, a qualitative diagnosis of coronary plaques using a 16 slice multidetector-row CT was conducted. METHODS AND RESULTS: Volume rendering and cross-sectional MPR images were obtained. Based on the CT values, plaques on the coronary artery wall were classified as lipid-rich soft plaques (CT value<50 HU) and non-soft plaques (>50 HU).A significant correlation was observed between the percent stenosis determined in cross-sectional MPR images and those determined by CAG (r=+0.92, p<0.01). Diffuse plaques with CT values of less than 50 HU often caused stenosis at level of 75% or less, which were not indicated by percutaneous transluminal coronary angioplasty. CONCLUSIONS: Although diffuse soft plaques with CT values less than 50 HU are not an indication of intervention, a risk of an acute coronary syndrome exists, due to rupture. These soft plaques must be stabilized by treatment even when they do not cause significant stenosis, and MDCT is considered to be useful for their evaluation.

Relationships between thermic effect of food, insulin resistance and autonomic nervous activity.

BACKGROUND: The thermic effect of food (TEF) is higher in lean than in obese human subjects. OBJECTIVE: Relationships between TEF and insulin resistance during meals, from the point of view of autonomic nervous activity, were evaluated. METHODS: Autonomic nervous activity was evaluated in 20 young adults using the spectral analysis of heart rate variability from one hour before to two hours after a meal. Heart rate data were analyzed based on low frequency components (LF power, 0.04-0.15 Hz), high frequency components (HF power, 0.15-0.40 Hz), and LF/HF ratios. Energy expenditure and the TEF were measured 30 min after a meal. Homeostasis model of insulin resistance index (HOMA-IR) was also measured. RESULTS: The LF/HF ratio was significantly increased 30 min after a meal (p<0.05). No correlation between LF power and HF power with TEF was found, but the LF/HF ratio was significantly and positively correlated with TEF (r=+0.56, p<0.05). Moreover, a significant negative correlation was found between the HOMA-IR and TEF (r=-0.601, p<0.05). CONCLUSIONS: The findings suggest that a reduction in insulin sensitivity induces a poor response of sympathetic nervous activity in the postprandial phase and a reduction in postprandial energy expenditure.

A patient with sustained ventricular tachycardia: identification of a responder to amiodarone using signal-averaged electrocardiogram.

A 75-year-old man suffered sustained ventricular tachycardia with syncopal attack. Ventricular tachycardias appeared repeatedly, and an electrical defibrillator was used after an anti-arrhythmic drug, such as lidocaine or mexiletine, proved ineffective. The tachycardias had multiple origins, and the signal-averaged electrocardiogram (SAECG) showed ventricular late potential before the administration of amiodarone. After administration, the filtered QRS and duration of the late potential increased, but the recurrence of tachycardias was suppressed. The reason for this is thought to be that amiodarone blocked the sodium channel and delayed conduction, consequently blocking reentry, because amiodaron has antiarrhymic properties with a prolongation of refractoriness and minimal effect on conduction velocity in ventricular myocardium, and inhibits sympathetic activity, and blocks L-type calcium channel besides the depression of the fast sodium channel. In this case, SAECG predicted to some degree whether or not this patient's ventricular tachycardia would respond to amiodarone.

Supplementation of L-arginine improves hypertension and lipid metabolism but not insulin resistance in diabetic rats.

Nitric oxide (NO) plays an important role in glucose and lipid metabolism. We previously reported that NO synthesis inhibitors, such as NG-nitro-L-arginine methyl ester (L-NAME), deteriorate insulin sensitivity and lipid metabolism, while the addition of L-arginine reverses this deterioration. L-arginine is a precursor of NO, and is used as a supplement in the US. In the present study, we evaluated whether the administration of L-arginine alone improves insulin resistance and serum lipid levels in insulin-resistant and hypertriglycemic rat models. Diabetic rats were divided into 3 groups: the control (Cont) group (standard diet), the L-NAME group (diet containing L-NAME), and the Arg group (diet containing L-arginine). After 4 weeks of breeding, urinary NOx, glucose infusion rate (GIR), glucose and lipid tolerance tests were performed. Urinary NOx levels were significantly lower in the L-NAME group than in the Cont group. The GIR in the L-NAME group was significantly lower than that in the Cont group, suggesting increased insulin resistance. However, the administration of L-arginine did not influence insulin resistance in the Arg group. Oral lipid administration significantly increased plasma triglyceride levels in the L-NAME group and plasma triglyceride levels were significantly lower in the Arg group than in the Cont group. The area under the curve of plasma triglyceride levels after oral lipid administration was larger in the L-NAME group than in the Cont group. The administration of L-NAME increased insulin resistance and decreased lipid metabolism. L-arginine significantly increased urinary NO secretion but did not improve insulin resistance, although it did improve lipid metabolism. These findings suggest that supplementation of L-arginine cannot improve insulin resistance in diabetic rats probably due to increased insulin secretion by L-arginine.

Effects of benidipine hydrochloride on autonomic nervous activity in hypertensive patients with high- and low-salt diets.

The effects of benidipine hydrochloride (CAS 91559-74-5, Coniel) on autonomic nervous activity in hypertensive patients with high- and low-salt diets were investigated. Six patients having a urinary sodium excretion of 80 mEq/day or less (low salt group) and 6 patients having a urinary sodium excretion of 200 mEq/day or more (high salt group) were orally given benidipine hydrochloride (4 mg). Before and four weeks after the treatment with benidipine, 24-h circadian variation in blood pressure and 24-h Holter electrocardiogram (ECG) were recorded. The low frequency power spectrum of heart rate (LF power; 0.04-0.15 Hz), high frequency power spectrum of heart rate (HF power; 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) were calculated, and these parameters were averaged every hour in every subject. HF power was significantly lower and LF/HF ratio was significantly higher in the high-salt group than in the low-salt group before the treatment. However, the benidipine treatment significantly increased the HF power in both groups, particularly in the high-salt group, and significantly decreased the LF/HF ratio in both groups. Moreover, there was no significant difference in the antihypertensive effect of benidipine between the high- and low-salt intake groups. These results suggest that benidipine favourably influences blood pressure and autonomic nervous activity in hypertensive patients with a high-salt intake. It is concluded that benidipine may be useful for improving the development of salt-induced hypertension and its accompanying haemodynamic responses.