Telmisartan Decreases Plasma Levels of Asymmetrical Dimethyl-L-Arginine and Improves Lipid and Glucose Metabolism and Vascular Function

Telmisartan is an angiotensin II receptor blocker (ARB) and also an activator of peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We investigated whether telmisartan improves vascular endothelial function in patients with essential hypertension with the production of endothelial nitric oxide synthase (eNOS) through PPAR-gamma.Telmisartan was administered to 15 patients with essential hypertension. To assess vascular function, asymmetric dimethylarginine (ADMA), an eNOS inhibitor synthesized by endothelial cells, and the pulse-wave velocity (PWV) were measured. The serum levels of lipid, glucose, and glycohemoglobin (HbA1c) were also evaluated before and after treatment. Telmisartan therapy significantly decreased the blood pressure and total- and LDL-cholesterol levels. HbA1c was also significantly improved but not in fasting plasma glucose. The serum levels of ADMA were significantly decreased (0.48 +/- 0.08 to 0.42 +/- 0.05 nmol/mL; P = 0.01). PWV values were significantly decreased by telmisartan from 1,822.5 +/- 352.3 to 1,661.5 +/- 299.8 cm/second (P = 0.04*). Telmisartan decreased PWV presumably via the activation of PPAR-gamma, suggesting that this agent improves vascular endothelial function via its pleiotropic effects, a mechanism that is different from its hypotensive effects.


Labeled anti-mucin antibody detectable by infrared-fluorescence endoscopy.

The goal of our study was to develop a method for molecular imaging of the gastrointestinal tract using an infrared fluorescence endoscope (IRFE) and antibodies labeled with an indocyanine green (ICG) derivative to detect cancerous tissue. The IRFE comprised an infrared endoscope equipped with excitation (710-790 nm) and barrier (810-920 nm) filters. We developed ICG-N-hydroxysulfosuccinimide ester (ICG-sulfo-OSu) and 3-ICG-acyl-1,3-thiazolidine-2-thione (ICG-ATT) as infrared fluorescent-labeling reagents, and anti-human carcinoembryonic antigen (CEA) antibody and MUC1 antibody were labeled with the ICG-derivatives. Freshly resected specimens of gastric cancer were observed by IRFE after reaction with ICG-derivative-labeled antibodies. Positive fluorescence was observed at the tumor location by IRFE, and the immunofluorescent images correlated well with the tumor sites. The immunofluorescence studies suggested that the intensity of the infrared fluorescence of the ICG-ATT-labeled MUC1 antibody is stronger than the ICG-sulfo-OSu-labeled MUC1 antibody. We concluded that specific antibodies for gastrointestinal cancer labeled with an ICG-derivative accompanied by a reinforcing agent and an optimal electronic device can generate a strong enough fluorescent signal to visualize cancer proteins.


Ultrasonographic comparison of gastric motility between diabetic gastroparesis patients with and without metabolic syndrome.

Diabetic patients with poor glycemic control or long standing disease often have impaired gastric motility. Recently, metabolic factors such as blood glucose have been reported as influencing gastric motility independently of autonomic neuropathy. Many diabetic patients have metabolic syndrome, which is strongly associated with coronary and other diseases. We investigated whether metabolic syndrome influences diabetic gastroparesis patients. We observed gastric motility ultrasonographically in diabetic gastroparesis patients including nine with and nine without metabolic syndrome. Both groups complained of upper abdominal symptoms when hospitalized to improve blood sugar control. All patients underwent upper gastrointestinal endoscopy to rule out gastric and duodenal lesions. All had autonomic neuropathy. Gastric motility was evaluated within 3 days after admission by transabdominal ultrasonography after a test meal. Gastric emptying was 45.0 +/- 13.7% in patients with and 39.1 +/- 11.9% in patients without metabolic syndrome, which was not statistically significant. Frequency of gastric contractions was 8.33 +/- 2.78 per 3 min in patients with metabolic syndrome and 7.44 +/- 2.13 per 3 min in the others, which was not statistically significant. The motility index, which involves antral contractility, was 3.21 +/- 2.18 in patients with metabolic syndrome and 2.80 +/- 1.87 in the others, which was not statistically significant. Metabolic syndrome did not appear to contribute to delayed gastric motility in diabetic gastroparesis.

Journal of Gastroenterology and Hepatology


Influence of Lipid Emulsion for the Hematocrit Value Measured With Continuous Hematocrit Monitor.

Continuous monitoring of hematocrit with a CRIT-LINE monitor (CLM) is used to prevent excess ultrafiltration during hemodialysis and continuous renal replacement therapy. The presence of substances affecting the scattering and absorption rates of multiple wavelengths of near infrared rays of CLM in the blood may affect the measured values with CLM. We examined the influences of lipid emulsion (LE) on hematocrit and relative blood volume (RBV) which were measured with CLM using an in vitro experimental model with human blood. Additions of 10% or 20% of LE increased the hematocrit measured by LCM and decreased the percent change of RBV in proportion to the dose. One percentage of 20% LE in the plasma increased the expected hematocrit measured with CLM by 2.9%. The decrease of initial hematocrit from 48.1% to 43.4% decreased the expected percent change of RBV from -3.4% to -3.7% with the addition of 1 ml of 20% LE to 100 ml blood. These findings indicate that additions of LE increase hematocrit that is measured with CLM in proportion to the dose of LE. Low levels of initial hematocrit will increase the degree of expected percent change of RBV. Attention should be paid to the influence of LE during monitoring with CLM.


A case of parathyroid hormone-related peptide producing gallbladder carcinoma presenting humoral hypercalcemia of malignancy

Humoral hypercalcemia of malignancy(HHM)を来したPTHrP産生胆嚢癌の1例

Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive.

腫瘍随伴症候群は扁平上皮由来の癌で報告が多いが胆嚢癌に合併した報告は少ない．筆者らは経過中に高カルシウム血症および血中PTHrP高値を認め，病理組織標本においてPTHrP免疫染色が陽性であった胆嚢癌の1剖検例を経験したので報告する．

The Japanese Journal of Gastro-enterology


Low-volume continuous hemodiafiltration with nafamostat mesilate increases trypsin clearance without decreasing plasma trypsin concentration in severe acute pancreatitis.

Continuous hemodiafiltration (CHDF) has recently been used for treatment of severe acute pancreatitis. CHDF is capable of eliminating small molecules from blood, but whether trypsin can be eliminated by CHDF is not clear. In this study, elimination of trypsin-like enzyme activity (TLE) and cationic trypsin-like immunoreactivity (TLI) using low-volume CHDF was examined at the first CHDF session in eight patients with severe acute pancreatitis. CHDF was performed with a polysulfone hemofilter (membrane area, 0.7 m2) and nafamostat mesilate, a protease inhibitor and anticoagulant, at a blood flow rate of 100 ml/min and a filtration and dialysis flow rate of 10 ml/min each. Before beginning CHDF, plasma TLE was 3.41 +/- 2.86 nmol/(ml.min), and TLI was 5,900 +/- 9,008 ng/ml. The average plasma clearances of TLE and TLI achieved by the circuit during the 12-hour therapy were 56.7 +/- 4.9 ml/min and 8.0 +/- 7.2 ml/min, respectively. The average plasma clearance of TLI into the waste fluid was 2.4 +/- 1.6 ml/min whereas TLE was below the measurable sensitivity. The plasma concentration of TLE and TLI remained unchanged. These results indicate that low-volume CHDF using nafamostat mesilate as an anticoagulant can increase trypsin plasma clearance. However, low-volume CHDF is not effective to eliminate the plasma trypsin concentration.


Relationship between mucin expression and preoperatie bile juice cytology in biliary tract carcinoma

The present study evaluated correlations between preoperative bile juice cytology and mucin expression of surgical specimens in biliary tract carcinoma. Twenty-five patients with biliary tract carcinoma surgically treated at our hospital, whose bile juice cytology had been evaluated before operation, were allocated to this study. Biliary cytology was classified into three categories based on the Papanicolaou classification. Immunohistochemical staining of tissues was performed using MUC1 and MUC2 monoclonal antibodies. Lesions showing MUC1 expression of ++ or higher and MUC2 expression of - were classified as Group A, and the remaining lesions as Group B. According to the epithelial site, preoperative cytology was highly correlated in Group A, while it was negative in Group B (p<0.05). In the advanced site of carcinomas, preoperative cytology tended to highly be positive in Group A, while it tended to be negative in Group B (p<0.05). These results suggest that the bile juice cytology results are affected by characteristics of mucin expression in the tissue. Based on the possibility that mucin expression correlates with the prognosis of each carcinoma, a positive cytological result suggests a poor prognosis for the carcinoma, which may be informative for predicting the post-operative courses and choosing treatments.

The Journal of Medical Investigation : JMI


Influence of leukocytapheresis therapy for ulcerative colitis on anemia and hemodynamics.

In Japan, leukocytapheresis (LCAP) therapy has been carried out for ulcerative colitis as an effective therapy with a low incidence of side-effects. In the present study, we serially investigated the influence of LCAP therapy on anemia and hemodynamics in patients with ulcerative colitis using a non-invasive method with a Crit-Line monitor (CLM) (Hema Metrics Inc., Salt Lake City, UT and Boston, MA, USA). We carried out LCAP on 10 patients with ulcerative colitis using a CS-100 Cellsorba EX LCAP filter in 34 courses of LCAP. The mean hematocrit value, which was measured using the Crit-Line monitor, was 21.8 +/- 0.2% (21.0-22.4%), which showed no significant changes after each LCAP therapy. The actual erythrocyte count, hemoglobin and hematocrit values decreased by 244 000/mm3, 0.7 g/dL and 2.1%, respectively, however, the differences were insignificant. These values corresponded to 7.8, 8.0 and 7.6% of the values before LCAP, respectively. There were no significant changes in systolic blood pressure, diastolic blood pressure, or heart rate during LCAP. The results of this study suggest that one course of LCAP does not exacerbate anemia, and it does not influence hemodynamics. However, considering the exacerbation of anemia in patients with severe ulcerative colitis caused by massive melena, monitoring with a less invasive Crit-Line monitor and a vital information monitor might be useful.


Influence of an artificial pleural effusion technique on cardio-pulmonary function and autonomic activity

Percutaneous treatment of hepatocellular carcinoma (HCC) located directly under the diaphragm is problematic because ultrasonic imaging is difficult, and the lung may be injured during the procedure. It has been reported that an infusion of 5% glucose solution into the thoracic cavity enables percutaneous treatment in such cases. However, the safety aspects of this have not been investigated. In this study, variations in heart rate and changes in circulatory and respiratory dynamics were examined during the infusion of artificial pleural effusion directly under the diaphragm in patients with HCC. The subjects were 13 patients with an HCC directly under the diaphragm. About 500 ml of a 5% glucose solution was infused into the thoracic cavity, and mean blood pressure, heart rate, and oxygen saturation were measured. Holter electrocardiography was simultaneously recorded to evaluate autonomic nerve function. To analyze variations in heart rate, the low-frequency waves (LF: 0.04-0.15 Hz), high-frequency waves (HF: 0.15-0.40 Hz, an index of parasympathetic nerve activity), and the LF/HF ratio (index of sympathetic nerve activity) were examined. The above parameters were measured before, during (when infusion of the half the planned volume was complete), and after infusion were compared. No significant changes in the mean blood pressure or heart rate were found. Oxygen saturation was significantly decreased during and after the infusion. The HF value was slightly higher after infusion and the LF value was significantly increased during infusion. The LF/HF ratio was significantly increased during infusion, and this increase persisted after infusion. The infusion of artificial pleural effusion had no effect on circulatory dynamics, but transiently affected respiratory functions. It was also revealed that infusion stimulated the parasympathetic nerves.


Visualization of cardiac dipole using a current density map: detection of cardiac current undetectable by electrocardiography using magnetocardiography.

A close relationship exists between electric current and the magnetic field. However, electricity and magnetism have different physical characteristics, and magnetocardiography (MCG) may provide information on cardiac current that is difficult to obtain by electrocardiography (ECG). In the present study, we investigated the issue of whether the current density map method, in which cardiac current is estimated from the magnetic gradient, facilitates the visualization of cardiac current undetectable by ECG. The subjects were 50 healthy adults (N group), 40 patients with left ventricular overloading (LVO group), 15 patients with right ventricular overloading (RVO group), 10 patients with an old inferior myocardial infarction (OMI group), and 30 patients with diabetes mellitus (DM group). MCGs were recorded with a second derivative superconducting quantum interference device (SQUID) gradiometer using liquid helium. Isopotential maps and current density maps from unipolar precordial ECG leads and MCGs, respectively, were prepared, and the cardiac electric current was examined. The current density map at the ventricular depolarization phase showed one peak of current density in the N group. However, in the OMI group, the current density map showed multiple peaks of current density areas. In the RVO group, two peaks of current densities were detected at the right superior region and left thoracic region and these two diploles appeared to be from the right and left ventricular derived cardiac currents, respectively. Moreover, there was a significant correlation between the magnitude of the current density from the right ventricle and the systolic pulmonary arterial pressure. The current density map at the ventricular repolarization phase in the N group showed only a single current source. However, abnormal current sources in the current density maps were frequently detected even in patients showing no abnormalities on isopotential maps in the LVO, DM, and OMI groups. The findings herein suggest that opposing dipoles of the ventricular depolarization and repolarization vectors were summed and evaluated as a single dipole in the electrocardiogram. However, MCG facilitated the detection of multiple dipoles because of its superior spatial resolution as well as difference in physical properties between magnetic and electrical fields. Our results suggest that MCG with a current density map is useful for detecting cardiac current undetectable by ECG in an early stage.


BCAA-enriched snack improves nutritional state of cirrhosis

A late evening snack improves the catabolic state in patients with advanced liver cirrhosis. We tested whether long-term (3 mo) late evening snacking that included a branched-chain amino acid (BCAA)-enriched nutrient mixture produces a better nutritional state and better quality of life than ordinary food in patients with hepatitis C virus-positive liver cirrhosis. In a multicenter, randomized study, 48 patients with liver cirrhosis received late-evening supplementation with the BCAA-enriched nutrient mixture or ordinary food, such as a rice ball or bread, for 3 mo. During the study period, each patient was instructed on energy and protein intake. Blood biochemical data, nitrogen balance, respiratory quotient, and health-related quality of life (Short Form 36 questionnaire) were evaluated at baseline and at the end of the study. Total and late-evening energy intakes were similar in the two groups at 3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were significantly improved by the BCAA mixture but not by ordinary food. The parameters of the Short Form 36 did not statistically significantly improve over 3 mo in either group. Long-term oral supplementation with a BCAA mixture is better than ordinary food in a late evening snack at improving the serum albumin level and the energy metabolism in patients with cirrhosis.


Gastric motility and autonomic activity during obstructive sleep apnea.


A patient with early syphilis complicated by fatty liver who showed an alleviation of hepatopathy accompanied by jaundice after receiving anti-syphilitic therapy

A 42-year-old male with visceral obesity and a fatty liver presented with hepatopathy accompanied by jaundice and was diagnosed to have early syphilis based on the results of standard serologic tests and clinical findings. Both the subjective and objective findings including hepatopathy were rapidly alleviated by anti-syphilitic therapy. Severe hepatopathy accompanied by jaundice used to be considered a rare complication. However, due to contemporary unhealthy lifestyle patterns characterized by hypernutrition and a lack of exercise the occurrence of fatty liver is now dramatically increasing. Our findings suggest that the occurrence of fatty liver can exacerbate the damage to the hepatic parenchyma due to a Treponema pallidum infection.


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

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. 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. 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.


Nateglinide with glibenclamide examination using the respiratory quotient (RQ).

The respiratory quotient (RQ) is useful for evaluating glucose and lipid metabolism in vivo. We previously reported that the RQ value, even after fasting, was high in diabetics being treated with sulphonylurea (SU), which might explain the accumulation of fat, leading to weight gain in such individuals. In the present study, we measured the RQ in type II diabetic patients who were being treated with a rapid-onset/short-duration insulinotropic agent, nateglinide, and compared it with those being treated with SU. A glucose tolerance test was performed in 20 patients with type II diabetes mellitus treated with nateglinide and in 14 patients treated with SU, and the RQ was simultaneously measured. The RQ values in the patients treated with nateglinide, were similar to those in healthy adults, but was lower than in those treated with SU. No weight gain was observed in patients treated with nateglinide. A significant weight gain was reported in subjects treated with SU, accompanied by an increase in RQ. However, weight gain was less frequent in diabetics treated with nateglinide.


Histochemical and immunohistochemical investigation of guanase and

Guanase is known as an enzyme released from the liver. Recently, cloning and sequencing of the guanase gene were reported. In addition, almost simultaneously, it was reported that an unknown protein that binds to neuronal and endocrine lethal(1)-discs large (NE-dlg), one of the membrane-associated guanylate kinase homologues (MAGUK) family proteins involved in synaptic connection between neurons, was cloned and named nedasin (NE-dlg associated protein), whose sequence was almost identical to that of guanase. We immunostained fresh frozen sections of surgically removed human liver, kidney, and small intestine with anti-nedasin antibody, and simultaneously performed histochemical staining for guanase for comparison. Histochemically, guanase activity was observed in the cytoplasm of hepatocytes and biliary epithelium on the liver, in the mucosal epithelium on the small intestine, and in the proximal tubule on the kidney. Immunohistochemically, a brown discoloration due to DAB oxidation was seen in the cytoplasm of hepatocytes and biliary epithelium on the liver, in the proximal tubule but in the distal tubule a little on the kidney, in the mucosal epithelium on the small intestine. The stained region of the liver and the small intestine were different from that of the kidney. The different staining properties dependent on the organs were considered to be due to different isozymes. The physiological significance of guanase may vary with the isozymes, further studies are considered necessary.

The Journal of Medical Investigation : JMI


Development of a clipped single-bag with bicarbonate replacement fluid to ensure proper mixing.

A clipped single-bag for bicarbonate replacement fluid was developed to ensure proper mixing before administering to the patient. Nonmixture can cause imbalances of electrolytes and pH, which is a key problem for the current double-bag type bicarbonate replacement fluid sets. To resolve this problem, this single bag properly mixes the solutions before use. The new bag consists of a clip that is placed in the middle to keep the two solutions separated and sealed. When the caregiver is ready to administer treatment, the bag is simply unfolded and the clip automatically detaches, releasing the fluids. Thereby, the bicarbonate fluids are effectively mixed. An optimal clip size with an outer diameter of 16 mm and thickness of 2 mm was determined using compression tests and drop tests. This bag may be a safer and more effective way to provide proper replacement fluid supply for both hemofiltration and hemodiafiltration.


Intestinal Behcet's disease with esophageal ulcers and colonic longitudinal ulcers.

Intestinal Behcet's disease in a 38-year-old woman was diagnosed because of the history of recurrent oral aphthous ulcers, erythema nodosum-like eruptions, genital ulcer, and endoscopic findings of esophageal and ileocolonic punched-out ulcers with colonic longitudinal ulcers. Esophageal lesions and colonic longitudinal ulcers are rarely seen in intestinal Behcet's disease. The ulcers of esophagus and ileocolon healed with 3 wk of treatment with prednisolone and mesalazine without any adverse effect. Mesalazine may decrease the total dose of prednisolone required to treat the disease.


Fab fragment labeled with ICG-derivative for detecting digestive tract cancer


Oral delivery of diclofenac sodium using a novel solid-in-oil suspension.

The present work reports on a new pharmaceutical formulation for oral delivery of diclofenac sodium (DFNa), a non-steroidal anti-inflammatory drug (NSAID). Although DFNa itself is water-soluble at neutral pH, it was readily suspended in soybean oil via complex formation with an edible lipophilic surfactant and a matrix protein. The resulting solid-in-oil (S/O) suspension containing stably encapsulated DFNa in an oil phase markedly reduced the risks for gastrointestinal ulcers upon oral administration even at the LD(50) level in rats (ca. 50 mg/kg DFNa). In addition, plasma concentration of DFNa upon administration of an S/O suspension was comparable with that of the aqueous counterpart at the same DFNa dose. These results indicate the potential use of S/O suspensions as novel oil-based pharmaceutical formulations for oral delivery of water-soluble drugs without causing severe mucitis.


Optimal Labeling Condition of Antibodies Available for Immunofluorescence Endoscopy

In recent years, labeled antibodies have been used for diagnostic imaging in many studies. In this study, we investigated the mode of binding in antibodies labeled with ICG derivatives newly developed for the diagnosis of microcarcinomas, and evaluated the optimal binding molar ratio between the labeling compounds and antibody. MUC 1 antibody and ICG derivatives (ICG-ATT and ICG-sulfo-OSu) were used. ICG derivatives non-covalently bound to the antibody were removed with ethyl acetate, and the ratio of ICG derivatives covalently bound to the labeled antibody was confirmed. During purification of the labeled antibody, the amount of each labeling compound reacting with 1 molecule of the antibody varied as follows: 4, 8, 16, and 32 molar equivalents. Subsequently, the intensity of fluorescence was evaluated by spectroscopy and infrared fluoroscopy. The ratio of residual ICG derivative labeling the antibody was 67.4% for ICG-ATT and 65.0% for ICG-sulfo-OSu. When fluorescent antibody labeled with ICG-ATT at an F/P ratio of 2.94 or 4.18 was used, specific and clear fluorescent images of the antigen were obtained. When ICG-ATT-labeled antibody at an F/P ratio of 6.50 or 6.75 was used, the fluorescence intensity decreased and the fluorescent images of antigen became unclear. It was found that the ICG-ATT-labeled antibody was a more specific and sensitive marker than ICG-sulfo-OSu-labeled antibody, and that lower binding molar ratios of ICG-ATT were more useful for labeling the antibody.


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

The thermic effect of food (TEF) is higher in lean than in obese human subjects. Relationships between TEF and insulin resistance during meals, from the point of view of autonomic nervous activity, were evaluated. 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. 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). 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.


Effects of thrombus suction therapy on myocardial blood flow disorders in males with acute inferior myocardial infarction.

Several studies have reported that the use of a distal protection device decreases the incidence of slow-flow and/or no-reflow in patients with myocardial infarctions. In the present study, we investigated the influence of a RESCUE/Thrombuster system and a PercuSurge GuardWire catheter on coronary microcirculation disorders in patients with acute myocardial infarction using the natriuretic polypeptide (ANP), the brain natriuretic peptide (BNP), and (99m)Tc-tetrofosmin myocardial scintigraphy (TF). The group consisted of a 77 patients with initial inferior myocardial infarction who had undergone emergency coronary angioplasty. The patients were randomly divided into: Group D (n=28), in which a direct stent alone was inserted, Group R/T (n=25), in which a stent was inserted after RESCUE system or a Thrombuster system was performed, and Group P (n=24), in which a stent was inserted after thrombus suction using a PercuSurge GuardWire catheter. Patients with coronary slow-flow/no-reflow were 3, 2 and 0 cases in Group D, Group R / T and Group P, respectively. In the present study, patients with good-reflow were enrolled in order to investigate the coronary microcirculation disorder in patients with visually similar coronary blood flow obtained in coronary angiography after percutaneous coronary reperfusion therapy. TF myocardial scintigraphy was performed 10+/-3 days after admission. Bull's eye images were divided into 8 sections, and each section was evaluated in 4 grades. The grade of each segment was regarded as the defect score. The results were compared with the database prepared based on bull's eye maps from 50 healthy adults in our hospital, and count areas of -2 x SD (standard deviation) or less were calculated as the extent score (%), reflecting the area in which myocardial blood flow was decreased. The extent and severity scores in Groups P and R/T were significantly lower than those in Group D. Coronary angiography at the chronic stage (6 months after surgery) showed the patency of the responsible vascular lesion in all patients. However, the ANP, BNP, cardiac index, and pulmonary capillary wedge pressure (PCWP) were significantly improved in Groups R/T and P, compared to Group D (p<0.01). These results suggest that the use of a RESCUE/Thrombuster system and a PercuSurge GuardWire catheter system in patients with acute inferior wall infarction improves coronary microcirculation disorders and acute- to chronic-phase cardiac function.


Efficacy of glimepiride on insulin resistance adipocytokines and atherosclerosis.

Plasma adiponectin levels increase after the administration of glimepiride. This unique effects would also be expected to improve other adipocytokines and have anti-atherosclerotic action in patients with metabolic syndrome. Thirty-four patients with type 2 diabetes mellitus who were administrated glibenclamide were randomly divided into two groups. In 20 patients glibenclamide was changed to glimepiride (GP group), and the administration of glibenclamide (GB group) was continued in 14 patients. Twelve patients receiving insulin therapy (INS group) were enrolled for comparison. The levels of plasma adiponectin, high sensitive-CRP, TNF-alpha, interleukin-6, homeostasis model assessment-insulin resistance (HOMA-IR), brachial-ankle pulse wave velocity (baPWV) and augmentation index (AI) were measured before and 28 weeks after the therapy. HOMA-IR in the GP group was significantly decreased compared to the GB group. Plasma adiponectin levels were significantly increased in the GP group but not in the other groups. TNF-alpha, interleukin-6 and high sensitive-CRP levels were significantly decreased in the GP group, but not in the other groups. The baPWV and AI levels did not change in either the GB or the INS group, but were significantly decreased in the GP group. Glimepiride appears to improve insulin resistance and atherosclerotic disorders.


(123)I-metaiodo-benzylguanidine myocardial scintigraphy in the Brugada-type ECG.

The degree of ST-segment elevation and amplitude of J waves, which may change in patients with the Brugada-type electrocardiogram (ECG) over time, are influenced by autonomic nervous activity and the administration of antiarrhythmic drugs. In the present study, we evaluated whether the shape of ST-segment elevation in patients with a Brugada-type ECG might alter the parameters of an 123I-MIBG myocardial scintigraphy and body surface signal-averaged ECG (SAECG). The subjects consisted of 12 patients with a Brugada-type ECG and 15 healthy volunteers (N group). The patients with a Brugada-type ECG were classified into the following 2 groups based on the type of ST-segment elevation: 6 patients with the coved type ST-segment elevation (C group), and 6 patients with the saddle-back type ST-segment elevation (S group). Planar and SPECT images were obtained 15 minutes (early images) and 3 hours (delayed images) after the administration of 123I-MIBG, respectively. In addition, the washout rate (% WR) of 123I-MIBG was obtained in a bull's eye map of the SPECT image. There were no significant differences in the early H/M ratio between the C and S groups. In the C group, however, there were some patients who showed a decreased accumulation or defect of 123I-MIBG in the planar and SPECT images. Furthermore, in contrast to the N and S groups, the C group showed a decreased delayed H/M ratio and increased % WR. SAECG did not show any significant differences between the S and C groups. These results of the present study suggest that the shape of ST-segment elevation may be associated with myocardial autonomic nervous function. In addition, the electric heterogeneity of the action potential in the right ventricular epicardial myocardium, which is frequently influenced by autonomic nervous activity, is closely associated with the development of Brugada syndrome.

The Journal of Medical Investigation : JMI


Expression analysis of a mouse orthologue of HSFY, a candidate for the azoospermic factor on the human Y chromosome

Heat shock transcription factor on Y (HSFY) is located in one of three candidate regions for azoospermic factor (AZF), AZFb on the Y chromosome. We and others have already revealed that some azoospermic males are missing the regions of the Y chromosome including HSFY. Previously, we showed that murine HSFY-like sequence [mHSFYL (Riken cDNA 4933413G11Rik)], which is the mouse orthologue of HSFY, is exclusively expressed in testis. The sequences encoding the presumed DNA-binding domain in HSFY and mHSFYL were found in other mammals such as dogs, cows and chickens. To elucidate mHSFYL expression in the testes in detail, we carried out in situ hybridization. mHSFYL was predominantly expressed in round spermatids. Furthermore, we clarified the intracellular distribution of mHSFYL in COS1 cells with HA- or GFP-tagged proteins. Both HA-mHSFYL and GFP-mHSFYL were located in the nucleus. Our results suggest that HSFY/mHSFYL may have evolutionarily conserved functions for spermatogenesis.


Evalution of episodes of sleep apnea in patients with liver cirrhosis

Obstructive sleep apnea syndrome (OSAS) has been reported to be a new complication of liver cirrhosis with ascites. This fact prompted a study of episodes of sleep apnea as a function of the severity of cirrhosis. Forty eight patients with type C liver cirrhosis were divided according to the Child-Pugh score into 3 groups: Group A (16 patients with grade A cirrhosis), Group B (16 patients with grade B cirrhosis), and Group C (16 patients with grade C cirrhosis). Portable sleep polygraphs (Fuji RC, Inc. Tokyo, Japan) were attached to the subjects, and oronasal respiration, tracheal sounds, respiratory movements of the chest, and percutaneous arterial oxygen saturation continuously were recorded. A decrease in the mean airflow to 50% or less was defined as hypopnea, and the number per hour of episodes of apnea and hypopnea per hour lasting 10 seconds or longer (AHI) was counted. A Holter ECG was also recorded, and spectral heart rate variability during sleep was analyzed by measuring low frequency power (0.04-0.15 Hz, LF power), high frequency power (0.15-0.40 Hz, HF power), the ratio of LF power to HF power (LF/HF ratio), and very low frequency power (0.008-0.04 Hz, VLF power). The difference in QT interval between the lead CM5 and the lead CM1 (QTc dispersion) was also examined. AHI was significantly higher in Group C than in Groups A and B (p<0.05). In Group C, 6 patients with 20 times or more AHI per hour, obstructive sleep apnea, in which respiratory chest movements occur but oronasal respiration decreases or disappears, was observed. Spectral analyses of heart rate variability showed a decrease in HF power without sleep apnea, but increases in HF power and VLF power were observed during sleep apnea. The QTc dispersion increased during episodes of sleep apnea. As the stage of liver cirrhosis advanced, sleep apnea appeared, and changes in autonomic nervous activities were observed. Furthermore, QTc dispersion was increased during episodes of sleep apnea, presumably increasing the risk of ventricular arrhythmia.


Relationship between adhesion molecules with hs-CRP and changes therein after ARB (Valsartan) administration in patients with obstructive sleep apnea syndrome

It has been reported that a relationship exists between obstructive sleep apnea syndrome (OSAS) and cardiovascular and cerebrovascular diseases. To address this issue, we evaluated whether OSAS is associated with adhesion molecules and inflammatory signs, important indicators of atherosclerosis. Levels of high-sensitivity CRP (hs-CRP) and intercellular adhesion molecule-1 (ICAM-1) were measured in 30 patients with ischemic heart disease, confirmed by coronary arteriography (IHD group). Twenty healthy volunteers without sleep apnea were used as controls (Group N). Sleeping respiratory information was collected using a portable sleep polygraph, together on information about oronasal flow, tracheal sound, chest respiration, and percutaneous oxygen saturation (SpO2) to obtain the apnea-hypopnea index (AHI). In the IHD group, 9 (30%) of the 30 patients showed evidence of OSAS [IHD(AHI> or = 40) group] and 21 did not [IHD(AHI<40) group]. The levels of hs-CRP and ICAM-1 were significantly higher in the IHD group than in the N group (p<0.01). Moreover, the levels of hs-CRP and ICAM-1 were significantly higher in the IHD(AHI > or = 40) group than in the IHD(AHI<40) group (p<0.01). However, after the administration of valsartan, angiotensin II receptor antagonists (ARB) to both IHD groups, the levels of hs-CRP and ICAM-1 decreased significantly in both groups. Moreover, a multivariate analysis revealed that the levels of hs-CRP and ICAM-1 were associated with the severity of sleep apnea. These findings suggest that, in OSAS the levels of hs-CRP and ICAM-1 are decreased and that the administration of ARB decreases the risk of atherosclerosis.


尋常性天庖瘡に伴う食道病変

尋常性天庖瘡に伴う食道病変


嚢胞変性により特異な形態を呈した胃GISTの一例

嚢胞変性により特異な形態を呈した胃GISTの一例


Colonic pseudolipomatosis, microscopically classified into two groups

Colonic pseudolipomatosis is rare and the pathogenesis is controversial. The purpose of the present paper was to clarify endoscopic and histological characteristics of colonic pseudolipomatosis and to discuss the etiology. A total of 15 lesions from 14 patients was reviewed. They were able to be histologically classified into two groups on the basis of variety in size of the vacuoles: Group A, the ratio of largest vacuole to smallest vacuole in size is less than three, Group B, the ratio is more than four. Four of 15 lesions were group A, and were endoscopically polypoid or flat lesions covered with normal-looking mucosa. They were microscopically characterized by (i) predominant location in the upper portion of the lamina propria; (ii) no submucosal involvement; (iii) less variation in vacuolar size; and (iv) no association with lymph follicles. The vacuoles of group A contained proteinaceous materials in two of four lesions. Group B (11 lesions) had small elevated mucosa with normal-looking surface or non-elevated reddish mucosa. Microscopically, the lesions were mainly located in the lower portion of the lamina propria, occasionally also in the submucosa, had variable-sized vacuoles, and were related to lymph follicles. It is suggested that the vacuoles in group A contain fluid, and may indicate an abnormal stagnation of interstitial fluid. Microscopic appearance of group B is essentially similar to that of pneumatosis coli. It is thought that group B probably results from penetration of gas from the crypts into the mucosa during colonoscopy. It is unclear why group B had a preference for ileocecal valve and an association with lymph follicles.

Journal of Gastroenterology and Hepatology


Adenomyomatosis of the Gallbladder as a Potential Risk Factor for Gallbladder Carcinoma


Duodenal lymphangitis carcinomatosa: endoscopic characteristics and clinical significance.

Duodenal lymphangitis carcinomatosa has been sporadically described, but so far little attention has been paid to duodenal lymphangitis carcinomatosa. Four cases with duodenal lymphangitis carcinomatosa were endoscopically and histologically examined. The four cases exhibited multiple polypoid lesions along the Kerckring's folds and/or were covered by characteristically granular, non-ulcerated mucosa upon thickening. The granularity seems to been caused by dilated lymph vessels containing the carcinoma cells. The lesions were microscopically characterized by: (i) involvement of lymph vessels located in the upper portion of the lamina propria; (ii) no inflammatory changes; and (iii) no desmoplastic changes. Primary sites were thought to be the stomach in case 1, the pancreas in cases 2 and 4, and unknown in case 3. All patients died within 6 months after admission or endoscopic examination. As duodenal lymphangitis carcinomatosis shows characteristic endoscopic appearance, endoscopic diagnosis is not difficult. We should realize that the lesion represents extremely poor prognosis, and it should be distinguished from ordinary metastatic duodenal carcinoma.


Low Volume Continuous Hemodiafiltration with Nafamostat Mesilate Increases Trypsin


Effect of azelnidipine on autonomic nerve activity in essential hypertension

本態性高血圧症におけるアゼルニジピンの自律神経活動に及ぼす影響についての検討


心肥大を合併する本態性高血圧患者におけるアゼルニジピンによる抗動脈効果作用および心肥大抑制作用の検討


Prediction of Prognosis in Gallbladder Carcinoma by Mucin and p53 Immunohistochemistry

Mucin core proteins are known to be present in various organs and are specifically expressed with carcinogenesis and closely associated with the prognoses of various malignant tumors in the digestive tract such as colorectal cancer. The present study evaluated correlations between mucin and p53 expression and prognosis of gallbladder cancer using surgically resected tissue specimens from 26 patients with gallbladder carcinoma surgically treated at our hospital. Immunohistochemical staining was performed using MUC 1, MUC2, and p53 monoclonal antibody. The level of antigen expression in the lesion was classified into four stages: none(-), slight(+), moderate (++), and severe (+ + +). According to the UICC classification, histopathological grading, levels of T, N, and M factors, and tumor stages were compared with regard to the correlations with mucin and p53 expression. All cases were classified into two groups according to the results of mucin immunohistochemistry: group A (MUC1, > or = ++; and MUC2, < or = +) and group B (MUC1, < ++; or MUC2, > +). Postoperative survival periods were compared between the two groups and p53-positive and -negative groups. Neither histological grading nor T factor correlated with mucin or p53 expression, respectively. Moreover, neither N factor nor M factor correlated with mucin or p53 expression. Furthermore, stage grouping did not correlate with mucin or p53 expression. However, when the correlation between the postoperative survival period and mucin expression was evaluated, the mean postoperative surgical period was significantly shorter in Group A than in Group B (1.02 years in Group A vs 2.92 years in Group B; P = 0.016). There was no relationship between postoperative survival period and p53 positivity. Mucin expression was independent of various tumor growth factors and clearly reflected the prognosis of gallbladder cancer. Because the relative malignancy of gallbladder cancer could be evaluated by examining the level of glycoprotein expression in tumor tissue, mucin could be a more important marker than p53 for predicting prognosis in gallbladder carcinoma using surgically resected tissue specimens.


The relationship between autonomic nervous activity and physical activity in children

There have been few studies that have reported on heart rate variability and the development of autonomic nervous function in children. This study investigated the relationship between heart rate variabilities at night and physical activity in children. The study subjects were 29 children, including 17 boys and 12 girls. The daily activity product and heart rate variabilities during sleep at night (00.00-05.00 hours) were measured and several aspects of these parameters were analyzed. In one child (an 8-year-old girl), heart rate variability and the physical activity product were measured for 12 days. There was a negative correlation between the mean R-R interval and the duration (min) of heavy exercise per day (r = -0.39, P < 0.05). In the 8-year-old girl, from whom data was obtained for 12 days, the duration of heavy exercise per day was negatively correlated with the mean R-R interval (r = -0.63, P < 0.05), the number of changes in successive R-R intervals greater than 50 msec (RR50) (r = -0.74, P < 0.01), and the high frequency (HF) component (r = -0.66, P < 0.05). Furthermore, the daily number of steps was negatively correlated with the mean R-R interval (r = -0.66, P < 0.05), RR50 (r = -0.71, P < 0.05) and the HF component (r = -0.66, P < 0.05). There was a negative correlation between the amounts of energy consumption and the mean R-R interval (r = -0.69, P < 0.05). There was a negative correlation between the amounts of energy consumption and RR50 (r = -0.76, P < 0.01). Moreover, there was also a negative correlation between the amount of energy consumption and the HF component (r = -0.71, P < 0.05). These findings suggested that physical activities increase heart rate during sleep, but reduce parasympathetic nervous activity at night. Because both the HF component and RR50 reduce with growth, the exercise-related inhibition of parasympathetic nervous activity may be a developmental stimulus to reach a balanced autonomic nervous pattern in adults.


Evaluation of gastric emptying by electrogastrography and ultrasonography in gastroesophageal reflux disease


Association of Inflammatory Marker and Highly Sensitive C-Reactive Protein With Aerobic Exercise Capacity, Maximum Oxygen Uptake and Insulin Resistance in Healthy Middle-Aged Volunteers

Increased levels of inflammation markers, such as C-reactive protein (CRP) and tumor necrosis factor-alpha , have been found in insulin resistance syndrome. Those with elevated levels of high-sensitive CRP (hs-CRP) are at a higher risk for coronary heart disease. In the present study, we evaluated whether maximum oxygen uptake and insulin resistance are related to hs-CRP for the primary prevention of coronary heart disease. The subjects were 50 subjects who did not have diabetes mellitus. A multi-step treadmill exercise test was performed to obtain the maximum oxygen uptake when assessed by computerized breath-by-breath analysis. As an index of insulin resistance, the homeostasis model insulin resistance index (HOMA-R; fasting glucose x fasting insulin/405) was used. In addition, bodyweight, body mass index, subcutaneous fat thickness, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. Multivariate analysis revealed that hs-CRP was significantly correlated with HDL-cholesterol, uric acid, gamma-glutamyl transpeptidase and maximum oxygen uptake. The maximum oxygen uptake showed the smallest odds ratio was in terms of the relationship with hs-CRP. The present study suggests that the development of exercising habits increases the maximum oxygen uptake. Furthermore, an elevated maximum oxygen uptake decreases HOMA-R and reduces the inflammatory marker CRP, suggesting that exercising habit plays an important role in the primary prevention of coronary heart disease.


Three-Dimensional Reconstruction of ENdosonographic Images of Gastric Lesions: Preliminary Experience

This study was conducted to assess the ability of the endoluminal sonographic probes to image upper gastrointestinal lesions detected with conventional endoscopy and to reconstruct 3-dimensional (3D) images. Sonographic images were obtained from 25 gastrointestinal lesions in 22 patients using a sonographic miniprobe manually drawn at a set speed across lesions detected during conventional endoscopy. 3D images were then reconstructed using an in-house software program. In 16 lesions (64%), the 3D sectional images were evaluated as good, and all 25 lesions (100%) could be visualized both transversely and longitudinally. In 12 lesions (48%), the 3D display of the endosonographic surface image corresponded to the endoscopic appearance. In all 11 cases of gastric cancer, the depth of tumor invasion measured using the 3D image was consistent with the histologic diagnosis (100% accuracy). When videotaped sonographic images were stored on a hard disk, it took an average of 3.5 minutes to obtain and display 3D images of the targeted area. 3D sonographic reconstructions of digestive lesions were useful in diagnosis, and we believe that further improvements should enhance the clinical usefulness of 3D endosonography.


A patient with octopus pot-shaped cardial cancer that metastasized to multipleorgans

A 71-year-old male was admitted for abdominal fullness. The condition rapidly deteriorated in a short period (3 weeks), and the patient died. Autopsy revealed a protruding lesion measuring about 3 cm with erosion measuring 5 mm in diameter immediately below the esophago-gastric conjugation site, suggesting primary cardial undifferentiated adenocarcinoma. In the primary focus, changes on the mucosal surface were almost normal However, below the mucosa, infiltration of cancer cells was observed in an approximately 3 cm area along the gastric wall. Simultaneously, the site of infiltration was markedly increased in deep areas. Extraserous infiltration was observed. The morphology was special, and resembled an octopus pot, a trap used to catch octopuses in Japan, with a narrow top and a broad base. In our patient, metastatic lesions were detected in multiple organs, including the stomach.

The Journal of Medical Investigation : JMI


Opposing effects of oestradiol and progesterone on intracellular pathways and activation processes in the oxidative stress-induced activation of cultured rat hepatic stellate cells.

Oxidative stress, including the generation of reactive oxygen species (ROS), is involved in hepatofibrogenesis. The authors' previous studies have shown that oestradiol suppresses hepatic fibrosis in animal models and attenuates the activation of cultured rat hepatic stellate cells (HSCs), which possess oestrogen receptor subtype beta and are also activated by ROS. To define the mechanisms by which female sex hormones play an antifibrogenic role in activated HSCs, the effects of oestradiol and progesterone on ROS generation processes and intracellular pathways, leading to the activation of HSCs undergoing oxidative stress, was examined. HSCs, isolated from rats, were cultured for 7 days with oestradiol or progesterone for 24 hours as pretreatment, and oxidative stress was then induced by exposure to low doses of hydrogen peroxide for another 24 hours. Oestradiol inhibited ROS generation and antioxidant enzyme loss via the suppression of NADH/NADPH oxidase activity, and attenuated hydrogen peroxide induced transforming growth factor-beta1 (TGF-beta1) expression, HSC proliferation and transformation, and the activation of mitogen activated protein kinase (MAPK) pathways and transcription factors. Progesterone exerted a stimulatory effect through the progesterone receptor on the induction of ROS generation processes and intracellular pathways, resulting in TGF-beta1 expression and HSC activation, and fibrogenic effects were inhibited by oestradiol. These findings show for the first time that oestradiol inhibits the activation of transcription factors by suppressing ROS generation processes and the MAPK pathways, and inactivates the downstream transcription processes involved in TGF-beta1 expression and HSC activation, whereas progesterone acts in opposition to the favourable effects of oestradiol and its effects are blocked by oestradiol.


A patient with adult extrahepatic portal obstruction, of which distinction from intrahepatic cholangiocarcinoma was difficult.

A 51-year-old Japanese male with chief complaints of slightly high fever and epigastralgia was hospitalized at our facility. The inflammatory response was enhanced, and liver dysfunction was observed. Abdominal ultrasonography demonstrated a hyperechoic lesion occupying the left portal vein, and abdominal plain CT indicated a low density of the lesion with a clear boundary, measuring about 3 cm x 2 cm, between the porta hepatis and segment IV of the liver. Contrast CT showed no enhancement in the arterial and portal phases, but a reduction in the density inside the tumor in the equilibration phase was noted. MRI showed hypointensity by T1-weighted imaging and hyperintensity by T2-weighted imaging. Angiography demonstrated an obstruction of the left portal vein and superior mesenteric vein, and endoscopic retrograde cholangiography revealed a constriction in the left intrahepatic bile duct. Since the possibility of intrahepatic cholangiocarcinoma could not be excluded, extended left hepatectomy combined with caudate lobectomy was performed. The tumor, measuring 31 mm x 21 mm x 20 mm, was pathohistologically diagnosed as an extrahepatic portal obstruction. Extrahepatic portal obstruction is an important disease that is sometimes difficult to rule out oncologic origin.


Relationship between pulse wave velocity and circulatory hemodynamics during upper gastrointestinal endoscopy


A Novel Diagnostic Method for Evaluation of Vascular Lesions in the Digestive Tract Using Infrared Fluorescence Endoscopy

We have developed an infrared fluorescence endoscope to evaluate gastrointestinal vascular lesions. Infrared endoscopy (IRE) after intravenous administration of indocyanine green (ICG) is used at present to examine vascular lesions such as esophageal varices. However, no previous study has compared the sensitivity of infrared fluorescence endoscopy (IRFE) with that of IRE. In this study, we compared the usefulness of IRFE and IRE. For IRFE we used an infrared endoscope equipped with excitation and barrier filters and an intensified charge-coupled device camera. In preliminary experiments, the observable tissue depth was assessed by wrapping increasing numbers of layers of commercially available pork around a syringe containing a uniform concentration of ICG or by changing the concentration of ICG in a syringe covered by a piece of pork of uniform thickness. In the clinical part of the study, ICG was administered intravenously at different concentrations to patients with esophageal varices and the resulting infrared fluorescent images were evaluated. The preliminary experiments revealed that the depth of tissue that could be visualized was significantly greater in IRFE than it was in IRE (11.2 mm in IRFE vs. approximately 3.2 mm in IRE). Clear infrared fluorescence was obtained by IRFE at lower concentrations of ICG than the concentrations required to obtain clear images using IRE. In the clinical part of the study, clear infrared fluorescence was observed in a region where esophageal varices had been detected by conventional endoscopy when ICG was administered in doses of 0.005 mg/kg to 0.01 mg/kg, which was lower than the doses used in IRE. Compared with conventional IRE, IRFE facilitated the observation of deeper layers, and esophageal varices were observed by IRFE following the intravenous administration of a markedly reduced dose of ICG. IRFE, in combining the characteristics of reflected infrared light and fluorescence, may be a useful novel procedure in the diagnosis of vascular lesions in the gastrointestinal tract.


最大酸素摂取量と血中ホモシステインとの関連性:トータル·ヘルス·プロモーション·プラン検診による検討

トータル·ヘルス·プロモーション·プランによる健康づくりにより，ホモシステイン濃度の低下がみられ，動脈硬化を減少させると考えられた．


Influence of large intrahepatic blood vessels on the gross and histological characteristics of lesions prpduced by radiofrequency ablation in a pig livermodel


A Treatment Using ST1571 for Jejunal Gastrointestinal Stromal Tumor (GIST) Accompanied with Liver Metastas and Peritoneal Dissemination

A 64-year-old man with a chief complaint of melena visited our emergency outpatient clinic. After several examinations, he was diagnosed as a gastrointestinal stromal tumor (GIST) with liver metastasis. Surgical resection of the jejunal lesion and postoperative adjuvant therapy with STI571 for one year was performed. Due to recent immunohistological studies and introduction of STI571, the diagnosis, treatment, and prognosis of GIST are about to change profoundly. Further accumulation of cases is necessary to investigate the diagnosis, treatment, and prognosis of GIST.


Losartan improves regional left ventricular systolic and diastolic function in patients with hypertension --- Accurate evaluation using a newly developed color-coded tissue Doppler imaging technique

Angiotensin II receptor antagonists have recently been accepted as antihypertensive therapy. Tissue Doppler imaging (TDI) has been developed as a noninvasive tool to assess quantitatively regional myocardial motion abnormalities. This study was designed to determine whether our newly developed technique of color-coded TDI may be a useful means of quantifying the improvement in regional left ventricular (LV) myocardial contractility and relaxation after treatment with losartan in patients with hypertension. Losartan (50 to 100 mg) was administered for 6 months to 37 previously untreated patients with essential hypertension. Averaged myocardial velocity profiles (MVPs) for color-coded TDI were recorded in the ventricular septum and LV posterior wall before and after treatment. Peak myocardial velocities and peak myocardial velocity gradients (MVGs) in the LV walls were determined during systole and early diastole. The plasma concentration of transforming growth factor (TGF)-beta1 also was measured in all patients. Blood pressure and plasma TGF-beta1 level decreased after initiation of losartan therapy. The LV mass index and LV meridional end-systolic wall stress also decreased after treatment with losartan. LV geometry changed from a pattern consistent with concentric hypertrophy to normal geometry in 10 patients and to a pattern consistent with concentric remodeling in 5 patients, and from concentric remodeling to normal geometry in 5 patients after treatment with losartan. The ratio of early to late diastolic filling for the transmitral flow velocity increased after losartan treatment. The peak systolic and early diastolic myocardial velocities and MVGs in the ventricular septum and LV posterior wall increased after treatment with losartan, although the values 6 months after treatment with losartan were still lower than those in normal individuals. There were good correlations between changes in plasma TGF-beta1 level and changes in systolic and early diastolic MVGs 6 months after losartan. However, there were no significant correlations between changes in the systolic blood pressure and LV end-systolic wall stress and changes in the TDI parameters. Losartan improves regional LV function in patients with hypertension. Our newly developed averaged MVP and MVG measurements may be useful for accurately evaluating regional LV myocardial contractility and relaxation in these patients.


Impairment of gastrointestinal motility by nitrate administration: evaluation based on electrogastrographic changes and autonomic nerve activity

Nitrates decrease the tone of the lower oesophageal sphincter, and may thus induce gastro-oesophageal reflux. In the present study, we evaluated electrogastrographic changes and heart-rate variability before and after the administration of nitrates. In 15 patients with chest pain treated with nitrates, electrocardiography and percutaneous electrogastrography were performed before and after administration of nitrates. Autonomic nervous system function was evaluated by spectral analysis of heart-rate variability and serial changes in low frequency and high frequency power, and the low frequency/high frequency ratio were compared. Electrogastrograms were analysed by obtaining peak power amplitudes and their dominant frequencies. After the administration of nitrates (isosorbide dinitrate), high frequency power, an index of parasympathetic nervous activity, was significantly decreased, whereas the low frequency/high frequency ratio, an index of sympathetic nervous activity, was significantly increased. The mean peak amplitude of the electrogastrogram significantly increased postprandially both before and after treatment. After isosorbide dinitrate treatment, however, mean peak amplitudes after a meal were significantly lower than those obtained before treatment. The mean dominant frequency of the electrogastrogram did not vary before and after treatment. The present study suggests that nitrates inhibit gastrointestinal motility by decreasing autonomic nervous activity.


Long Term Follow-up in Japanese Public Office Workers of the Influence of Blood Pressure on ECG Changes

The relationship between annual changes in blood pressure (BP) and the electrocardiogram (ECG) was studied to clarity what factors give early detection of complications and predict the outcome of therapy. The influence of BP on the ECG was assessed in 830 Japanese office workers. Those with hypertension (HT) more frequently developed left atrial and ventricular overload compared with normotensive subjects. In addition, those with borderline HT (systolic pressure 140-160 mmHg and/or diastolic pressure 90-95 mmHg) and even those with lower blood pressure (systolic pressure 130-140 mmHg and/or diastolic pressure 85-90 mmHg) developed left atrial and ventricular overload more frequently than normotensive subjects. Based on these results, BP should be closely followed up when routine systolic and diastolic pressure levels exceed 130 mmHg and 85 mmHg, respectively, in persons in their 40 s to 50 s and the goal of antihypertensive therapy should be lower than reported previously.


A patient with Wallenberg's syndrome induced by severe cough

A 45-year-old man developed severe cough with cervical pain. The patient was unable to hold an upright position. The origin of the right posterior inferior cerebellar artery was not enhanced by angiography. MRI showed a high signal intensity string-like structure of the right vertebral artery. In young patients, Wallenberg's syndrome related to mild head trauma has been reported. However, none of the previous studies related to vertebral arterial dissection was induced by severe cough. When cervical pain is present in young patients with severe cough, MRI should be performed to evaluate the possibility of vertebral arterial dissection.


Antioxidant and antiapoptotic activities of idoxifene and estradiol in hepatic fibrosis in rats.

Oxidative stress plays a causative role in the development of hepatic fibrosis and apoptosis. Estradiol (E2) is an antioxidant, and idoxifene is a tissue-specific selective estrogen receptor modulator. We have previously demonstrated that E2 inhibits hepatic fibrosis in a rat model of hepatic fibrosis induced with dimethylnitrosamine (DMN), and suppresses activation of the nuclear factor (NF)-kappaB proinflammatory transcription factor in cultured rat hepatocytes undergoing oxidative stress. This study reports on the antioxidant and antiapoptotic role of idoxifene and E2 in the DMN model of hepatic fibrosis. The DMN model rats were administered with idoxifene or E2, and were examined activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and expression of Bcl-2 family proteins in the liver. During the course of hepatofibrogenesis after DMN treatment, serum levels of lactate dehydrogenase (LDH), a biomarker for necrosis, and hepatic levels of malondialdehyde (MDA), an end product of lipid peroxidation, increased rapidly for 3 days. On day 14, serum LDH levels normalized, and hepatic fibrosis developed with increased levels of MDA and collagen and decreased production of SOD and GPx in the liver. Fibrotic liver also showed downregulation of Bcl-2 and Bcl-X(L) expression and upregulation of Bad expression. Idoxifene and E2 suppressed DMN-mediated necrosis, lipid peroxidation, the loss of antioxidant enzyme activity, and proapoptotic status in Bcl-2 family protein expression as well as hepatic fibrosis. These findings indicate that, in addition to their antiinflammatory and antifibrotic action, idoxifene and E2 could enhance antioxidant and antiapoptotic activity in hepatic fibrosis in rats.


Colorectal xanthomas with polypoid lesion:report of 25 cases.

Little attention has been paid to colorectal xanthoma. To clarify the clinical and pathological features of colorectal xanthoma, we report 28 colorectal xanthomas biopsied from 25 patients. All were composed of typical xanthoma cells and showed polypoid configuration. Median age of the patients was 64 years and there were 15 men and 10 women. Diabetes mellitus, constipation, and hyperlipidemia were found in two, one, and seven patients, respectively. Seventeen (60.7%) of the 28 polyps were located in the sigmoid colon and the remaining 11 in the rectum. Twenty-three polyps (82.1%) were sessile. Twelve (60.0%) of twenty polyps that were recorded were reddish in color. Only two polyps revealed a yellowish tone. Microscopically, foamy cells were present in the lamina propria, but the submucosa did not contain foamy cells. Immunohistochemically, the foamy cells invariably expressed extensive positivity for CD68. The colonic glands showed a deformity in the case with moderate to intense density of the foamy cells. The surface epithelium showed a hyperplastic change in 22 (78.6%) xanthomas. The colonic glands in four xanthomas were also associated with hyperplastic changes. The basement membrane of the surface epithelium was often thickened. Cell debris and proliferation of the capillaries were observed just below the surface epithelium in 19 (67.9%) and 22 (78.6%) xanthomas, respectively. Previous mucosal minute injury was suggested as the pathogenesis of colorectal xanthomas. Colorectal xanthomas were not identical to gastric and esophageal xanthoma, endoscopically or microscopically. We prefer the term "xanthomatous polyp" rather than xanthoma in the colorectal region. They may be regarded as a novel type of colorectal non-neoplastic polyp.


Detection of coronary arterial microvascular discorders using 99mTc-tetrofosm in uptake increase during exercise and coronary blood flow velocity patterns obtained by magnetic resonance imaging.

This study reports an evaluation of coronary arterial blood flow patterns in patients with diabetes mellitus and healthy subjects using magnetic resonance coronary angiography (MRCA). Twenty patients with diabetes mellitus (DM group) and 20 healthy subjects (N group) were studied using MRCA and myocardial SPECT images using (99m)Tc-tetrofosmin (TF). The rate of change in myocardial TF uptake was measured during a 1-day protocol of exercise and rest. Initial and delayed exercise single photon emission computed tomography (SPECT) images were acquired 30 min and 3 h after injection (370 MBq of TF) (TF1 and TF2, respectively). Thereafter, 740 MBq of TF was administered intravenously, again, and resting SPECT images (TF3) were acquired 30 min later. The myocardial counts of these three points of acquisition were defined, and the rate of change of myocardial TF uptake between exercise and rest was determined. The % increase in uptake was significantly lower in the DM group than in the N group in all myocardial segments. The average coronary arterial diastolic velocity determined using MRCA was slightly lower in the DM group than in the N group, and the average systolic peak velocity (ASPV) was slightly greater in the DM group than in the N group, although these values were not statistically significant. The diastolic/systolic velocity ratio (DSVR) in the DM group was significantly lower than that in the N group ( P < 0.05). There was a significant correlation between DSVR and % uptake increase ( r = 0.605, P < 0.05). These results indicate that the measurements made using MRCA and the % uptake increase measured using TF myocardial scintigraphy represent a potentially useful noninvasive method for diagnosing microvascular dysfunction in diabetic patients.


Potential application of tissue Doppler imaging to assess regional left ventricular diastolic function in patients with hypertrophic cardiomyopathy: Comparison with 123I-β-methyl iodophenyl pentadecanoic acid myocardial scintigraphy.

Tissue Doppler imaging (TDI) has been utilized to evaluate left ventricular myocardial dysfunction in patients with hypertrophic cardiomyopathy (HCM); however, no clear explanation for the abnormality of TDI variables has been forthcoming. Peak negative myocardial velocity gradient (MVG) derived from TDI may correlate with a disorder of fatty acid metabolism in patients with HCM. Tissue Doppler imaging and 123I-beta-methyl iodophenyl pentadecanoic acid (123I-BMIPP) myocardial scintigraphy were performed in 15 patients with asymmetric septal hypertrophy (mean age 47 +/- 18 years) and in 12 healthy controls (mean age 43 +/- 10 years). In early 123I-BMIPP images, accumulation defects were observed in the ventricular septum in 12 patients and in the posterior wall in 8 patients with HCM. Peak negative MVG in the ventricular septum (1.1 +/- 0.5 vs. 2.8 +/- 0.5, p < 0.0001) and posterior wall (5.2 +/- 1.4 vs. 6.7 +/- 0.8, p < 0.01 ) was significantly lower in the HCM group than in the controls; also, these parameters were significantly lower in patients with than in those without a defect in the region in question. The peak negative MVG in the ventricular septum and posterior wall correlated inversely with the washout rate in all subjects. Peak negative MVG according to TDI is related to disorder of fatty acid metabolism in the regional left ventricular myocardium of patients with HCM.


Influence of sleep apnea on autonomic nervous activity and QT dispersion in patients with essential hypertension and old myocardial infarction

Sleep apnea syndrome (SAS) is an important cardiovascular risk factor in patients with hypertension or myocardial infarction (MI). We evaluated the influence of SAS on autonomic nervous activity and QT dispersion in patients with hypertension or coronary artery disease with old MI. A portable sleep polygraph was attached to 30 healthy volunteers (N group), 30 patients with essential hypertension (HT group), and 30 patients with old myocardial infarction (MI group) to serially record oronasal respiration, tracheal sound, thoracic respiratory movement, and percutaneous arterial oxygen saturation. In addition, a digital Holter ECG was used to examine heart rate variability during nighttime sleep. Heart rate variability was analyzed by obtaining low-frequency (LF) power, high-frequency (HF) power, the LF/HF ratio, and very low-frequency (VLF) power. Dispersion of QT intervals was obtained by CM5 and CM1 leads. VLF and LF powers were significantly higher in the HT-SAS group (hypertensive patients with SAS) than the N and HT-NSAS groups (hypertensive patients without SAS). The HF power was significantly lower in the HT-NSAS group than the N group, but the decrease in HF power in hypertension was not observed in the HT-SAS group. The LF/HF ratio was significantly higher in the HT-NSAS group than the N group, and this value was further increased in the HT-NSAS group. Percutaneous arterial oxygen saturation was decreased, and QT dispersion was significantly increased in the MI group during sleep apnea episodes. More severe autonomic nervous dysfunction and increased QTc dispersion were observed in hypertensive patients with SAS during episodes of apneas and hypopneas compared to those without SAS. These findings suggest that SAS may be associated with the future development of cardiac events.


Evaluation of myocardial sympathetic nerve function in patients with mitral valve prolapse using iodine-123-metaiodobenzylguanidine myocardial scintigraphy.

Mitral valve prolapse (MVP) is closely related to myocardial sympathetic nerve function. This study evaluated the presence of impaired myocardial sympathetic nerve function by Iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy in ten patients with MVP. For comparison, 15 healthy subjects without heart disease were investigated (control group). Single photon emission computed tomography (SPECT) and anterior planar myocardial scintigraphy were performed 15 min (initial images) and 3 hours (delayed images) after injection of MIBG (111 MBq). The location and degrees of reduced tracer uptake were evaluated. Myocardial MIBG uptake was quantified by uptake ratio of the heart (H) to upper mediastinum (M) on the anterior planar images (H/M). Percentage washout of MIBG in nine sectors of all oblique slices along the short-axis was calculated. The washout rates were higher at the inferoposterior and septal segments in patients with anterior leaflet prolapse, and at inferoposterior and lateral segments in patients with posterior leaflet prolapse. The bull's eye map showed increased washout rate in the apical and posteroseptal basal segments. There was no significant difference in the H/M ratio between MVP patients and the control group. These results indicate that MIBG can be used to evaluate localized myocardial sympathetic nerve function in MVP.


心磁図法は循環器病診療に貢献できるのか?

心磁図法は循環器病診療に貢献できるのか?

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


Does Coronary Artery Stenting for Acute Myocardial Infarction Improve Left Ventricular Overloading at the Chronic Stage?

In the present study, we evaluated whether stenting is useful for cardiac overloading, using ANP, BNP, and sup99m/supTc-tetrofosmin myocardial scintigraphy. It has been reported that coronary artery stenting is useful for cardiac functions for acute myocardial infarction (AMI). The subjects were 110 patients with AMI successfully treated by direct angioplasty. These patients were subgrouped into two groups: the S group (underwent stenting; 54 patients) and the P group (underwent POBA alone; 56 patients). Extent scores reflecting decreased myocardial blood flow were calculated at myocardial areas showing a radioactivity count of less than -2 × standard deviations compared to the database of normal subjects.The ratio of extent scores to defect scores (extent/defect ratio) was compared between the P and S groups. Both ANP and BNP levels in the S group were lower than in the P group at the chronic stage (1 and 3 months after reperfusion therapy). Moreover, the end-diastolic volume index from the left ventriculography 3 months after reperfusion therapy was significantly larger in the P than the S group. The extent/defect ratio was significantly lower in the P group (2.8 ± 0.2) than the S group (3.5 ± 0.3), suggestive of a microcirculation disorder. These results suggest that cardiac overloading and left ventricular remodeling are decreased more by stenting than by POBA alone, probably because stenting prevents decreased myocardial blood flow around the infarct myocardium.br


Clinical Study on the Effects of Nizatidine on Gastric Motillity and Cardiac Autonomic Function

Nizatidine (CAS 76963-41-2, Acinon), an H2 receptor antagonist, not only inhibits acid secretion but also improves gastrointestinal motility. However, autonomic nervous function has not been studied in detail using electrogastrography (EGG). In the present study, two protocols were adopted to study nizatidine's effects on cardiac autonomic function and gastric motility. Protocol I--Acute: "Group C-I": 10 healthy volunteers received a single oral dose of nizatidine 150 mg. Protocol II--Chronic: "Group DM without N": 15 patients with diabetes mellitus (DM) were observed prior to administration of nizatidine. "Group DM with N": The same 15 patients with DM received nizatidine 300 mg/day for more than 30 days. "Group C-II": This control group was composed of 15 healthy volunteers not receiving nizatidine. In all groups, EGGs were recorded before and after a meal, and autonomic nervous function and QT interval of ECG dispersions were simultaneously evaluated. In Group C-I, nizatidine significantly increased the peak power amplitude of 3 cycles/min (cpm) frequency, but did not significantly change the dominant frequency of the 3-cpm waves. In Group DM with N, nizatidine administration significantly increased the peak power amplitude from 2.4 cpm or a lower frequency (bradygastria) to 3 cpm. Prior to nizatidine administration but after eating a meal, the peak power amplitude on EGG was not increased in Group DM without N. In Group DM with N, however, the EGG peak power amplitude increased to levels similar to those of the healthy subjects (Group C-II). Neither the single nor the chronic administration of nizatidine significantly prolonged the QT interval or increased the QT dispersion. A spectral analysis of heart rate variability showed that nizatidine administration, whether acute or chronic, did not significantly change the indices of autonomic nervous activity. Nizatidine may promote gastric emptying by inhibiting acetylcholine esterase, thus increasing cholinergic activity, and by acting directly on gastric smooth muscle. The results indicate that because nizatidine increases gastric motility without exerting a negative influence on the autonomic nerves, it may be a useful drug in patients with diabetic neuropathy.


胃X線検査時における体位変換時の自立神経活動の変動 --- 心拍変動解析による検討

日本消化器集団検診学会雑誌

日本消化器集団検診学会雑誌


高速フーリエ解析を用いた圧波形解析によるフィルタの目詰まり評価

高速フーリエ解析を用いた圧波形解析によるフィルタの目詰まり評価


Inhibitory effect of a soluble transforming growth factor β type II receptor on the activation of rat hepatic stellate cells in primary culture

Oxidative stress, including the generation of reactive oxygen species (ROS) that acts as a signaling mediator for transforming growth factor (TGF)-beta, plays a key role in hepatic fibrosis. Hepatic stellate cells (HSCs) produce and respond to TGF-beta in an autocrine manner with increased collagen expression. It has previously been reported that the adenovirus-mediated overexpression of a soluble receptor against the extracellular domain of the TGF-beta type II receptor prevents hepatofibrogenesis in vivo, although its inhibitory role and mechanism in HSC activation remains to be elucidated. In this study, we report on an examination of the actual role of TGF-beta inhibition on oxidative stress and the activation of cultured rat HSCs, using the adenovirus-mediated soluble TGF-beta type II receptor. This soluble receptor secreted from the adenovirus-infected cells binds to TGF-beta. Infection of HSCs with this adenovirus attenuated intracellular levels of TGF-beta1 mRNA and protein, NADH oxidative activity, ROS generation and lipid peroxidation, and prevented HSC activation. These findings suggest that this adenovirus-mediated soluble TGF-beta receptor may lead to an interruption of the TGF-beta autocrine loop in activated HSC, in part, by inhibiting oxidative stress.


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 Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Neuropathy and Gastroparesis

Diabetic patients with severe autonomic nervous disorder show delayed gastric emptying accompanied by diabetic gastroparesis, which decreases the electric activity of the stomach associated with gastric motility. It is reported that epalrestat, an aldose reductase inhibitor, is useful for treating diabetic neuropathy. Therefore, we evaluated whether this drug improves the decreased gastric motility in diabetic patients. The present study evaluated the electrogastrograms (EGG) and autonomic nervous activity in 15 healthy volunteers (N group), and in 15 diabetic patients before and after the administration of epalrestat (DM group). Autonomic nervous activity was evaluated by spectral analysis of heart rate variability. The EGGs were recorded before and after oral administration of epalrestat (3 months or more) in the DM group. The dominant frequency of EGG was 3 cycles/min (cpm) in the N group. However, these 3 cpm waves disappeared with bradygastria, and postprandial increases in the peak powers of EGG were not observed in the DM group. Both the amplitude of 3 cpm waves and the postprandial peak powers were significantly increased after the administration of epalrestat. The parameters of autonomic nervous activities (LF power, HF power, and the LF/HF ratio) were significantly lower in the DM group before the administration of epalrestat than in the N group. However, these parameters were improved after the administration of epalrestat. Since gastroparesis is a form of diabetic dysautonomia, complication by gastroparesis may influence blood sugar control and the absorbance of oral antidiabetics. Epalrestat significantly increased the amplitude of 3 cpm waves on EGG and improved the spectral analytical parameters of heart rate variability. These findings suggest that epalrestat is useful for the treatment of diabetic gastroparesis.


A New Infrared Fluorescent-Labeling Agent and Labeled Antibody for Diagnosing Microcancers

We have developed infrared fluorescent labeling agents and infrared-ray fluorescence endoscopes to establish a novel diagnostic technique. Since the fluorescence intensity of the initial labeled antibody (ICG-sulfo-OSu-labeled antibody) was not sufficient for practical use, we synthesized indocyanine green acylthiazolidinethione (ICG-ATT), which was expected to label various target molecules having amino groups efficiently. To confirm imaging of infrared fluorescence intensity of ICG-ATT- and ICG-sulfo-OSu-labeled anti-MUC1 antibodies, cotton thread was soaked in various concentrations of the antibody solution in 0.1M PBS, and observed under the epi-illumination infrared fluorescence microscope. Localization and the intensity of infrared fluorescence and DAB coloring was compared in paraffin sections of human gastric mucosa. In the study of cotton threads, both labeled antibodies showed relatively clear infrared fluorescence, and significant difference was not observed between the two antibodies. ICG-ATT-labeled anti-MUC1 antibody produced stronger staining than that by ICG-sulfo-OSu-labeled antibody. Localization pattern of infrared fluorescent staining was in good agreement with that by the conventional method with oxidized DAB staining. ICG-ATT is useful as a fluorescent-labeling agent for diagnosis of microcancers by infrared fluorescence endoscopes.


Comparison of gastric peristalsis inhibition by scopolamine butylbromide and glucagon:evaluation by electrogastrography and analysis of heart rate variability

Activation of glucagon receptors of the smooth muscle membrane suppresses gastric peristalsis. We evaluated autonomic nervous activity by two methods, electrogastrography (EGG) and analysis of heart rate variability, to compare the inhibiting effects of glucagon and scopolamine butylbromide on gastric peristalsis. Heart rate variability, EGG, and blood catecholamine levels were measured before and after administration of glucagon (G group), scopolamine butylbromide (SB group), or physiological saline (C group). Autonomic nervous function was evaluated using spectral analysis of heart rate variability, and low frequency (LF) and high frequency (HF) power; the LF/HF ratios were also determined. After administration of scopolamine butylbromide, HF power, an index of parasympathetic nervous activity, decreased; and the LF/HF ratio, an index of sympathetic nervous activity, increased. In contrast, no significant change was observed in autonomic nervous activity after administration of glucagon. The peak power amplitudes of the EGG decreased significantly in the G and SB groups after intramuscular injection, but the difference between the groups was not significant. Furthermore, the dominant frequency increased significantly in the G and SB groups after injection. Serum catecholamine levels showed no significant changes after administration of scopolamine butylbromide or glucagon. Inhibition of gastric peristalsis by glucagon via glucagon receptors on smooth muscles did not influence autonomic nervous activity, unlike the results obtained after administration of scopolamine butylbromide. Therefore, glucagon may be safe for use with elderly patients and those with cardiopulmonary complications.


Autonomic nervous dysfunction in patients with liver cirrhosis using 123I-metaiodobenzylguanidine myocardial scintigraphy and spectrum analysis of heart-rate variability

Journal of Gastroenterology and Hepatology


High-sensitivity C-reactive protein and left ventricular remodeling in patients with acute myocardial infarction

Inflammatory cytokines are suspected to play an important role in the pathophysiology of left ventricular (LV) remodeling. We investigated whether high-sensitivity C-reactive protein (CRP) (hs-CRP) is a predictor for LV remodeling in patients with acute myocardial infarction (AMI) with successful reperfusion, and also whether such a situation can be avoided by the administration of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). The subjects were 139 patients with an initial attack of anterior myocardial infarction successfully treated by reperfusion therapy. They were randomly divided into the following two groups: an angiotensin (AG) group (91 patients treated with ACEI/ARB) and a NON-AG group (48 patients not treated with ACEI/ARB). Levels of hs-CRP, creatine kinase, human atrial natriuretic polypeptide, brain natriuretic peptide (BNP), fasting blood glucose, serum lipids, fibrinogen, fibrin degradation product, prothromloin time, and activated partial thromboplastin time were measured immediately after 1, 2, 3, and 7 days, and 1 months after the onset of AMI. ACEI or ARB administration lowered hs-CRP levels and prevented the development of LV remodeling. Peak CRP levels significantly correlated with BNP levels during the acute stage (r = +0.54, P < 0.0001), end-diastolic volume index (r = +0.78, P < 0.0001), end-systolic volume index (r = +0.36, P = 0.0405), ejection fraction (r = -0.45, P = 0.0052), left ventricular end-diastolic diameter (r = +0.61, P < 0.0001), cardiac output (r = -0.52, P = 0.0005), cardiac index (r = -0.41, P = 0.0099), and systolic pulmonary arterial pressure (r = +0.48, P = 0.0017) 1 month after the onset of AMI in the NON-AG group but not in the AG group. Logistic multivariate analysis revealed that peak CRP alone was an independent risk factor for the development of LV remodeling in the NON-AG group (odds ratio = 1.79, P = 0.002). These results suggest that hs-CRP is a useful factor for predicting LV remodeling. Furthermore, ACEI or ARB administration to AMI patients showing increased hs-CRP levels during the early stage of the disease could prevent LV remodeling.


Myocardial perfusion magnetic resonance imaging for diagnosing coronary arterial stenosis:evaluation by signal-intensity time curves

It has been reported that myocardial perfusion MRI is a useful method for evaluating the severity of myocardial ischemia. We evaluated whether the severity of coronary arterial stenosis could be assessed by the signal-intensity time curve (SITC) obtained by myocardial perfusion MRI.br The subjects consisted of 10 patients who showed no abnormalities on coronary angiographies (CAG) (A group), 12 with single-vessel disease of 75-90% stenosis on CAG (B group), and 15 with single-vessel disease of 90% or more stenosis (C group). After infusion of dipyridamole for 4 minutes, gadolinium-diethylenetriamine pentaacetic acid was administered intravenously, followed by serial acquisition of T1-weighted left ventricular short-axis MR images. These images were evaluated after dividing them into the following 3 myocardial segments: anterior wall, lateral wall, and inferior wall. Mean values of the slope of SITC (1.4 ± 0.2 vs 1.1 ± 0.2, iP /i 0.01), and increases to the peak corrected SI (ΔSI) (47.5 ± 1.9 % vs 33.7 ± 2.4%, iP/i 0.01) in normal myocardial segments were significantly greater than in ischemic segments in the C group, while there was no significant distinction between normal and ischemic segments in the B group. The mean values of time to the peak SI were not significantly different between normal and ischemic regions in the B and C groups.br The results suggest that myocardial segments exhibiting 30% decreases in both the slope and ΔSI of SITC can be diagnosed as having 90% or more severe coronary stenosis. The present study shows that visual and SITC evaluations of myocardial perfusion MR images may be useful for clinically evaluating the severity of coronary stenosis.br


Novel approach to the quantitation of regional left ventricular systolic and diastolic function using tissue Doppler imaging to create a myocardial velocity profile and gradient

The myocardial velocity profile (MVP) and gradient (MVG) between the endocardium and epicardium of the left ventricular (LV) wall measured by color-coded tissue Doppler imaging (TDI) are new indices for evaluating regional LV myocardial function. However, accurate recording and measurement of the MVP is difficult using conventional methodology because of the stochastic nature of the ultrasound signal; that is, the effect of speckled noise. The aim of this study was to validate the accuracy and establish the validity of a newly developed method for measuring the MVP and MVG using 10 clinically normal controls and 10 patients with a hypertensive hypertrophied LV posterior wall. A non-isotropic, averaging algorithm was developed that was capable of obtaining a stable MVP (averaged MVP). Averaged MVP was recorded using parasternal, LV short-axis, color-coded TDI, placing regions of interest along the LV posterior wall with the reference point for angle-correction being at the center of LV contraction. The velocity from epicardium to endocardium within the region of interest was automatically angle-corrected to calculate the velocity component radially relative to the LV cavity and was spatially averaged along the circumference within the region of interest. Inter- and intraobserber variabilities of measurements were lower in the averaged MVP and MVG than in the conventional MVP and MVG. The correlation coefficients of the linear regression lines of systolic and early diastolic MVPs in the LV posterior wall were higher in all controls and hypertensive patients with the averaged method than with the conventional TDI procedures. The mean peak systolic and early diastolic MVGs were lower in the hypertensive group than in the controls. In conclusion, the newly developed averaged MVP provides a stable and reproducible index for the quantitative assessment of regional LV myocardial function.


Prognostic value of the atrial systolic mitral annular motion velocity in patients with left ventricular systolic dysfunction.

Transmitral flow velocity variables are powerful predictors of poor prognosis in patients with left ventricular (LV) systolic dysfunction. However, these variables may not accurately reflect the severity of pulmonary congestion. This study was designed to determine whether the peak atrial systolic mitral annular motion velocity (MA-Aw) measured by pulsed Doppler tissue imaging can predict cardiac death or hospitalization for worsening heart failure in patients with LV systolic dysfunction. MA-Aw was recorded in 96 patients with LV systolic dysfunction who were followed up for 29 +/- 10 months. All patients underwent Doppler echocardiography on entry into the study, and cardiac catheterization was performed in 45 patients. Patients were divided into 3 groups on the basis of the ratio of early (E) to late (A) diastolic filling (E/A) of the transmitral flow velocity: group 1 (n=31; E/A < 1); group 2 (n=37; 1 < or = E/A < 2); and group 3 (n=28; E/A > or = 2). During follow-up, 36 patients (38%) died of cardiac causes and 34 (35%) were hospitalized for worsening heart failure. There were 2 cardiac deaths (6%) in group 1, 14 (39%) in group 2, and 20 (56%) in group 3. The MA-Aw correlated closely with the mean pulmonary capillary wedge pressure. Univariate Cox model analysis showed that MA-Aw < or = 5 cm/s was the most powerful predictor of cardiac death or hospitalization for worsening heart failure compared with clinical, hemodynamic, and the other echocardiographic variables. Furthermore, MA-Aw < or = 5 cm/s was clearly discernible as a good predictor of cardiac mortality on multivariate Cox model and as assessed by Kaplan-Meier method. The MA-Aw obtained by pulsed Doppler tissue imaging is a sensitive index of pulmonary congestion in patients with LV systolic dysfunction. It is a simple and noninvasive outcome measure and can be used to monitor treatment.

Journal of the American Society of Echocardiography


Idoxifene and Estradiol Enhance Antiapoptotic Activity Through Estrogen Receptor- in Cultured Rat Hepatocytes

Oxidative stress plays a causative role in the development of hepatic fibrosis and apoptosis. Estradiol (E2) is an antioxidant, and idoxifene is a tissue-specific selective estrogen-receptor modulator. We have previously demonstrated that E2 inhibits hepatic fibrosis in rat models of hepatic fibrosis and that the actions of E2 are mediated through estrogen receptors (ERs). This study reports on the antiapoptotic role of idoxifene and E2, and the functions of ER subtypes ER-alpha and ER-beta in hepatocytes undergoing oxidative stress. Lipid peroxidation was induced in cultured rat hepatocytes with ferric nitrilotriacetate solution with idoxifene or E2. Oxidative stress-induced early apoptosis was linked to its ability to inhibit not only the expression of Bcl-2 and Bcl-XL but the production of antioxidant enzymes as well and to stimulate Bad expression. Hepatocytes possessed functional ER-beta, but not ER-alpha, to respond directly to idoxifene and E2. Idoxifene and E2 suppressed oxidative stress-induced reactive oxygen species generation and lipid peroxidation, and their antiapoptotic effects on the activation of activator protein-1 and nuclear factor-kappaB, the loss of antioxidant enzyme activity, and Bcl-2 family protein expression in early apoptotic hepatocytes were blocked by the pure ER antagonist ICI 182,780. Our results indicate that idoxifene and E2 could enhance antiapoptotic activity through ER-beta during oxidative damage in hepatocytes.


肝細胞アポトーシスにおけるエストラジオールとエストロゲン受容体βの抑制的関与

肝細胞アポトーシスにおけるエストラジオールとエストロゲン受容体βの抑制的関与

Japanese Journal of Medicine and Pharmaceutical Science


Basic study of an agent for reinforcement of near-infrared fluorescence on tumor tissue

An indocyanine green derivative (ICG-sulfo-OSu) and agents for reinforcement of infrared fluorescence, which can be used as an infrared fluorescent labeling substance suitable for detection of microlesions by an IR fluorescence endoscope, have been developed. The study aims were to confirm the ability of a reinforcement agent, as well as imaging processing, to intensify fluorescence from the labeled antibody on immunohistochemical staining. ICG-sulfo-OSu-labeled MUC1 antibody and an IR fluorescence imaging system were employed in the present study. Paraffin sections of gastric cancer were stained with anti-MUC1 antibody by the avidin-biotinylated peroxidase complex method. Among the positive specimens, three cases were used for IR imaging analysis. Octylglucoside was used as a reinforcement agent. The incubation of paraffin sections with ICG-sulfo-OSu-labeled MUC1 antibody resulted in positive staining of the tumor sites by an IR fluorescence imaging system, and the intensity of fluorescence was increased depending on the concentration of octylglucoside and grade of imaging processing. A reinforcement agent, and image processing, intensify a labeled antibody excitable by infrared fluorescence in tumor sections and can generate a strong enough fluorescent signal to detect small cancers when examined with an infrared fluorescence endoscope.