Treatment of multiple rectal carcinoids by endoscopic mucosal resection using a device for esophageal variceal ligation.
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Carcinoid Tumor↗
Biomedical subjects
M Fujii
Publications and source records attributed to M Fujii.
Anti-tumour effects of nobiletin, a citrus flavonoid, on gastric cancer include: antiproliferative effects, induction of apoptosis and cell cycle deregulation.
AIM: To demonstrate the antitumour effects of nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), a citrus flavonoid extracted from Citrus depressa Hayata, on human gastric cancer cell lines TMK-1, MKN-45, MKN-74 and KATO-III. MATERIALS AND METHODS: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the TdT-mediated dUTP biotin nick-end labelling (TUNEL) method and cell-cycle analysis revealed that nobiletin acted on these cells in several ways, namely by direct cytotoxicity, induction of apoptosis and modulation of cell cycle. The efficacy of combined treatment of nobiletin with a conventional anticancer drug, CDDP, was also examined. Treatment with nobiletin 24 h prior to CDDP administration showed a synergistic effect compared to the control. CONCLUSIONS: Although the effective dose and administration route of nobiletin require further investigation, our study represents a potential successful linking of this compound with the treatment of gastric cancer.
Anticarcinogenic Agents↗
Unusual hypersensitivity to warfarin in a critically ill patient.
A patient was admitted to the intensive care unit because of respiratory failure, and warfarin therapy was started at 2 mg/day for the treatment of pulmonary embolism, together with other medications. Despite the low dosage of warfarin, international normalized ratio (INR) was markedly elevated from 1.15 to 11.28 for only 4 days, and bleeding symptoms concurrently developed. Vitamin K2 was infused along with discontinuation of warfarin. One day later, the INR was found to have decreased, and bleeding was also improved. An objective causality assessment indicated a probable relationship between clotting abnormality and warfarin administration, although the degree of elevation of the INR was unusual in the light of the daily warfarin dose and duration of its exposure. Based on the clinical status of the patient, it was suspected that several conditions contributed to the abnormal hypersensitivity to warfarin. Contributory factors probably included pharmacokinetic interactions with co-administrated drugs, vitamin K deficiency caused by decreased dietary intake, reduced gut bacterial production, impaired intestinal absorption and hepatic synthetic capacity, and increased consumption of clotting factors. In view of our experience in the present case, it should be stressed that close monitoring of coagulation capacity is necessary in critically ill patients in order to avoid fatal haemorrhage after initiating warfarin therapy regardless of the dosage.
Aged↗
Changes in serum leptin concentrations in overweight Japanese men after exercise.
AIM: To investigate the link between serum leptin concentrations and exercise. DESIGN: Cross-sectional and longitudinal studies of an exercise intervention. SUBJECTS: 110 Japanese overweight men aged 32-59 years were recruited. At baseline, the average body mass index (BMI) was 28.5 +/- 2.5 kg/m2. From this group, we used data of 36 overweight men (BMI, 28.9 +/- 2.3) for a 1-year exercise programme. MEASUREMENTS: Leptin was measured at baseline and after 1 year. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical levels. Anthropometric parameters, aerobic exercise level, muscle strength and flexibility were also investigated at baseline and after 1 year. RESULTS: In the first analysis, using cross-sectional data, leptin was significantly correlated with total body fat (r = 0.760, p < 0.01), V (r = 0.383, p < 0.01) and S (r = 0.617, p < 0.01) areas. In the second analysis, using longitudinal data, leptin was significantly reduced after 1 year (pre 6.7 +/- 4.0 ng/ml vs. post 5.1 +/- 3.1 ng/ml, p < 0.01). Results showed that steps per day were increased, and aerobic exercise level, weight-bearing index (WBI) and insulin resistance were significantly improved. Although, there was a positive correlation between Delta leptin(positive changes in leptin after 1 year) and anthropometric measurements such as Delta body weight, Delta BMI and Delta body fat, leptin/body weight, leptin/BMI and leptin/body fat ratios were significantly reduced during exercise intervention. CONCLUSION: The present study indicated exercise significantly lowers serum leptin concentrations, and thus it may improve the leptin resistance observed in overweight Japanese men.
Adult↗
Nicorandil versus isosorbide dinitrate as adjunctive treatment to direct balloon angioplasty in acute myocardial infarction.
OBJECTIVE: To compare the effects of nicorandil (a hybrid ATP sensitive potassium channel (K+(ATP) channel) opener/nitric oxide donor) with those of isosorbide dinitrate (ISDN) on myocardial microcirculation and cardiac function in patients with acute myocardial infarction (AMI) who had undergone reperfusion treatment by direct balloon angioplasty. DESIGN: Double blind randomised study. PATIENTS: 60 patients with AMI in Killip class I. INTERVENTIONS: Patients were assigned into two treatment groups: a nicorandil group (n = 30) and an ISDN group (n = 30). Each drug was infused intravenously at 6 mg/h for 72 hours starting at admission and was administered directly to the treated coronary artery immediately after angioplasty. RESULTS: Compared with ISDN, nicorandil more frequently caused recovery of ST segment elevation just after reperfusion (15 of 27 (55.5%) in the nicorandil group v 5 of 26 (19.2%) in the ISDN group, p = 0.006). The nicorandil group had higher values of averaged peak velocity 40 minutes after reperfusion (mean (SD) 24.8 (13.3) cm/s v 16.0 (11.1) cm/s, p = 0.045) and higher values of regional wall motion of the infarcted area three weeks after onset of AMI (-1.78 (1.11) v -2.50 (1.04) SD/chord, p = 0.046). CONCLUSIONS: A combination of nicorandil drip infusion starting before reperfusion and intracoronary injection immediately after reperfusion is more effective than a similarly performed infusion of ISDN in preserving myocardial microcirculation in the reperfused AMI area. The nicorandil regimen resulted in better left ventricular regional wall motion.
Angioplasty, Balloon↗
Relationship between transcardiac gradient of endothelin-1 and left ventricular remodelling in patients with first anterior myocardial infarction.
Aims To evaluate whether plasma endothelin-1 (ET-1) is extracted or produced through the heart in patients with acute myocardial infarction (AMI), and the relationship between transcardiac extraction of plasma ET-1 and left ventricular (LV) remodelling. Methods and results We measured the plasma level of ET-1 in the aortic root (Ao) and coronary sinus (CS) in 48 consecutive patients, who received successful revascularization and enalapril, for a first anterior AMI. In the acute phase the plasma ET-1 level was significantly higher both in the Ao and the CS compared to the control subjects. However, the plasma ET-1 level was significantly lower in the CS than in the Ao in the acute phase and after 1 month. There were significant correlations between transcardiac extraction of ET-1 in the acute phase and LV ejection fraction and LV end-diastolic volume index (LVEDVI) after 1 month. Stepwise multivariate analysis showed that maximal creatine phosphokinase and transcardiac extraction of plasma ET-1 during the acute phase were independently and positively correlated with the absolute change in LVEDVI after 1 month. Conclusions These results indicate that elevated circulating ET-1 is extracted through the heart in patients with a first anterior AMI and that the extracted ET-1 plays a significant role in modulating post-infarct LV remodelling.
Atrial Natriuretic Factor↗
Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education.
OBJECTIVE: To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO(2) and work rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: In total, 30 Japanese overweight men (BMI, 29.0+/-2.2 kg/m(2)) and 31 normal-weight men (BMI, 22.5+/-1.6 kg/m(2)) at baseline were enrolled: 30 overweight men (BMI, 29.0+/-2.2 kg/m(2)) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months. RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r=0.350, P=0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r=-0.619, P<0.001), S (r=-0.457, P<0.001) and V areas (r=-0.466, P<0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.0+/-2.2 to 28.0+/-2.0, P<0.001), V and S areas, increase in VO(2) and WR at VT, increase in bFGF (9.21+/-5.82-21.2+/-7.04 ng/ml, P<0.001), and no change in VEGF (1.45+/-0.72-1.88+/-0.52 ng/ml, P=0.016). The stepwise multiple regression analysis revealed that DeltaBMI (beta=-6.052) and DeltaVO(2) (beta=2.806) were independently related to DeltabFGF (P<0.001) and all other variables including DeltaS area, and DeltaV area, and DeltaWR did not enter the equation at significant levels. CONCLUSION: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DeltaBMI and DeltaVO(2) with DeltabFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.
Adipose Tissue↗
In vitro expansion of human basophils by interleukin-3 from granulocyte colony-stimulating factor-mobilized peripheral blood stem cells.
BACKGROUND: A number of studies support the belief that human basophils play an important role in allergic inflammation. The exact mechanism of basophil activation at the site of allergic inflammation, however, has not been well understood, mainly due to their low number in blood and difficulty in obtaining a sufficient number of highly purified basophils for investigation. OBJECTIVE: The purpose of this study is to expand human basophils in vitro with high yield and purity by culturing peripheral blood stem cells (PBSCs). METHODS: We collected PBSC-rich mononuclear cells containing CD34+ cells (0.15-4.9%) by leukapheresis from patients with malignant lymphoma and lung cancer during haematopoietic recovery after chemotherapy plus granulocyte colony-stimulating factor-induced mobilization. PBSC-rich mononuclear cells were cultured in the presence of IL-3. RESULTS: When PBSC-rich mononuclear cells containing more than 1% of CD34+ cells were cultured, 20.0-83.3% of the cells, mostly with a yield of >10%, were metachromatic cells after 3 weeks of culture. These cells resembled mature peripheral blood basophils morphologically when examined by light and electron microscopy. Flow cytometric analysis showed that they expressed both FcepsilonRI and FcgammaRII. FcepsilonRI cross-linking resulted in intracellular calcium mobilization, histamine release and synthesis of cysteinyl leukotrienes. The intracellular histamine content and the release of these chemical mediators triggered by anti-IgE antibodies were comparable to those of peripheral blood basophils. CONCLUSION: These findings suggest that PBSC-derived basophils expanded in vitro are morphologically and functionally mature and will be a useful tool for the analysis of basophil functions.
Adolescent↗
The association between end-stage diabetic nephropathy and methylenetetrahydrofolate reductase genotype with macroangiopathy in type 2 diabetes mellitus.
The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene polymorphism is associated with elevated homocysteine levels and presumably with increased atherosclerotic risk. We evaluated the interaction between this gene polymorphism and end-stage diabetic nephropathy on the observed prevalence of macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80 with and 94 without renal failure due to diabetic nephropathy. In the patients with renal failure, the T/T genotype and T allele were significantly associated with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P = 0.00014), whereas the associations were not significant in the patients without renal failure. In the multiple logistic regression analysis, age (10 years OR 4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P = 0.0013) were significantly associated with macroangiopathy in the patients with renal failure. In conclusion, this study demonstrated that the 677 T/T genotype and T allele of MTHFR were significantly associated with macroangiopathy in type 2 diabetic patients with renal failure. The MTHFR 677 T allele, together with renal dysfunction due to diabetic nephropathy, could be a strong risk factor for atherosclerotic disease.
Aged↗
[Intrathoracic chronic expanding hematoma; report of a case].
A case of a patient with a intrathoracic chronic expanding hematoma presenting as a neoplasm is reported. A chronic encapsulated intrathoracic hematoma is rare condition and is clinically included in a category of chronic hemorrhagic empyemas as a type of chronic empyemas in Japan. The clinical picture of our case suggested a slowly growing tumor. Though needle biopsy was performed, only blood was aspirated. Intraoperative findings revealed a intrathoracic hematoma with a tough capsule. It adhered to the chest wall hardly. Histopathological investigations revealed that the capsule consisted of a collagenous outer layer and a newly vascularized inner layer with fibrosis. Hemosiderin deposits suggested recurrent bleeding from fragile vessels. The mechanisms of hematoma formation and its expanding nature are discussed. The hematoma appeared to have been enlarged by repeated exudation or bleeding from capillaries inside the capsule.
Chronic Disease↗
Critical point of body fat percentage in obese Japanese.
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Adult↗
Stimulated light emission in dense fog confined inside a porous glass matrix.
We report on light amplification through stimulated emission in a dielectrically disordered medium. Liquid fragments confined in the solid matrix of porous quartz layers result in a random fluctuation of the dielectric function, and dye molecules embedded in the voids yield optical gain. The level of opacity is tunable by the ambient vapor pressure of the dielectric substance. In the multiple scattering regime, a strong intensity enhancement of the dye emission accompanied by significant spectral narrowing is observed above the threshold for a layer being in the opalescence state.
Journal Article↗
Resonant electronic energy transfer from excitons confined in silicon nanocrystals to oxygen molecules.
We demonstrate efficient resonant energy transfer from excitons confined in silicon nanocrystals to molecular oxygen (MO). Quenching of photoluminescence (PL) of silicon nanocrystals by MO physisorbed on their surface is found to be most efficient when the energy of excitons coincides with triplet-singlet splitting energy of oxygen molecules. The dependence of PL quenching efficiency on nanocrystal surface termination is consistent with short-range resonant electron exchange mechanism of energy transfer. A highly developed surface of silicon nanocrystal assemblies and a long radiative lifetime of excitons are favorable for achieving a high efficiency of this process.
Journal Article↗
The effect of ethanol on the simultaneous transport and metabolism of methyl p-hydroxybenzoate in excised skin of Yucatan micropig.
The effects of ethanol on the simultaneous transport and metabolism of methyl p-hydroxybenzoate (HBM) were investigated in the skin of Yucatan micropig in vitro. It was found that transesterification occurred in the permeation studies involving ethanol. This was confirmed by monitoring the flux of ethyl p-hydroxybenzoate (HBE) into the receptor phase, as well as by monitoring the fluxes of HBM and p-hydroxybenzoic acid (HBA). The apparent flux of total HBM was decreased. The solubility of HBM increased with ethanol concentration, thus, the activity of HBM in ethanol solution became low because we used 10 mM HBM solution for permeation studies. The enhancement factor (E) was calculated to correct the activity. E increased with increasing the flux of ethanol, thus, ethanol may function as an enhancer of HBM transport. The hydrolysis of HBM to HBA was inhibited, whereas transesterification of HBM to HBE was induced at all concentrations of ethanol used (10-40%). The formation of HBE occurred much more readily than that of HBA at all concentrations of ethanol used.
Animals↗
Enhancement of skin permeation of miconazole by phospholipid and dodecyl 2-(N,N-dimethyl amino)propionate (DDAIP).
Miconazole (MCZ) has very low solubility in both water and oil. Permeation rates through shed snakeskin from an aqueous suspension and a mineral oil suspension were 0.5 microg/cm(2)/h and almost none, respectively. When hydrogenated phosphatidylcholine (HPC) was added to mineral oil and heated to 95 degrees C, the solubility of MCZ increased in proportion to the HPC concentration. DSC measurements also indicated an interaction between them. Thus, a gel formed by hydrogenated phospholipid and mineral oil, as vehicle was prepared. The solubility of MCZ in the gel was around 1% and the permeation rate was 1.3 microg/cm(2)/h, which was about 2.5 times that from an aqueous suspension. As an alternative approach, a skin permeation enhancer, dodecyl 2-(N,N-dimethyl amino)propionate (DDAIP) was applied 2 h before a skin permeation study. The permeation from an aqueous suspension became 11 times that of the suspension without DDAIP pretreatment. The concentration of MCZ in the skin increased 8-fold, indicating that the enhancement effect involved high partition of MCZ into the skin. On the other hand, when a gel formulation was used, pretreatment with DDAIP was not as effective as incorporation of DDAIP in the gel formulation. Following pretreatment, permeation was only two times that of the gel without DDAIP pretreatment, and half that of the water suspension with DDAIP pretreatment. This suggested that release from the gel was the rate-limiting step with the gel formulation. When DDAIP was added to the gel, the permeation rate of MCZ was 3.3 microg/cm(2)/h. It was also a release limited type permeation. The gel with DDAIP is potentially a useful formulation, because of relatively high permeation while possibly avoiding overdosing.
Alanine↗
Relationship between reduced serum IGF-I levels and accumulation of visceral fat in Japanese men.
OBJECTIVE: To investigate whether the changes in IGF-I concentrations after weight reduction in Japanese overweight men are associated with changes in visceral and subcutaneous fat. DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: One-hundred and twelve Japanese overweight men aged 30-59 y (body mass index (BMI) 28.4+/-2.5 kg/m(2)) and 33 normal-weight men aged 30-39 y (BMI 22.1+/-1.5 kg/m(2)) at baseline. From the participants, 56 randomly selected overweight men (BMI 28.8+/-2.8) were further enrolled into a 1 y exercise program. MEASUREMENTS: Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, metabolic parameters and hormones including insulin, leptin and IGF-I at baseline and after 1 y. RESULTS: In 112 overweight subjects at baseline, insulin (10.5+/-5.0 microU/ml) and leptin (6.4+/-3.7 ng/ml) significantly correlated with both V (r=0.260, P=0.0073; r=0.410, P<0.0001) and S areas (r=0.377, P<0.0001; r=0.613, P<0.0001), respectively. IGF-I (156.8+/-48.7 microU/ml) significantly and negatively correlated with V area (r=-0.242, P=0.0125) and age (r=-0.192, P=0.0480). In normal-weight men aged 30-39 y (n=33) and age-matched subjects (n=30) selected from the 112 overweight men, the serum IGF-I further tightly correlated with V area (r=-0.467, P<0.0001). Visceral fat area and age were independently related to serum IGF-I levels by multiple regression analysis. By intervention with exercise education, 56 overweight subjects showed an increase in daily steps (6224+/-2781 to 7898+/-4141 steps/day) and reduction of BMI (28.8+/-2.8 to 27.7+/-2.9). deltaIGF-I significantly correlated with deltaV area (r=-0.432, P=0.0009) but not with DeltaS area or deltaBMI. CONCLUSION: The present study indicated a negative correlation between IGF-I levels and visceral fat at baseline as well as an association between the reduction in visceral fat and increase in IGF-I levels after an exercise intervention.
Adipose Tissue↗
High-dose intravenous immune globulin for stiff-person syndrome.
BACKGROUND: Stiff-person syndrome is a disabling central nervous system disorder with no satisfactory treatment that is characterized by muscle rigidity, episodic muscle spasms, high titers of antibodies against glutamic acid decarboxylase (GAD65), and a frequent association with autoimmune disorders. Because stiff-person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin. METHODS: We assigned 16 patients who had stiff-person syndrome and anti-GAD65 antibodies, in random order, to receive intravenous immune globulin or placebo for three months, followed by a one-month washout period and then by three months of therapy with the alternative agent. Efficacy was judged by improvements in scores on the distribution-of-stiffness index and heightened-sensitivity scale from base line (month 1) to the second and third month of each treatment phase. Direct and carryover effects of treatment were compared in the two groups. RESULTS: Among patients who received immune globulin first, stiffness scores decreased significantly (P=0.02) and heightened-sensitivity scores decreased substantially during immune globulin therapy but rebounded during placebo administration. In contrast, the scores in the group that received placebo first remained constant during placebo administration but dropped significantly during immune globulin therapy (P=0.01). When the data were analyzed for a direct and a first-order carryover effect, there was a significant difference in stiffness scores (P=0.01 and P<0.001, respectively) between the immune globulin and placebo groups, and immune globulin therapy had a significant direct treatment effect on sensitivity scores (P=0.03). Eleven patients who received immune globulin became able to walk more easily or without assistance, their frequency of falls decreased, and they were able to perform work-related or household tasks. The duration of the beneficial effects of immune globulin varied from six weeks to one year. Anti-GAD65 antibody titers declined after immune globulin therapy but not after placebo administration. CONCLUSIONS: Intravenous immune globulin is a well-tolerated and effective, albeit costly, therapy for patients with stiff-person syndrome and anti-GAD65 antibodies.
Adult↗
Relationship between transcardiac extraction of aldosterone and left ventricular remodeling in patients with first acute myocardial infarction: extracting aldosterone through the heart promotes ventricular remodeling after acute myocardial infarction.
OBJECTIVES: The purpose of this study was to evaluate whether plasma aldosterone (ALD) is extracted or produced through the heart in patients with acute myocardial infarction (AMI) and to determine the relationship between transcardiac extraction of plasma ALD and left ventricular (LV) remodeling. BACKGROUND: Although we demonstrated that circulating ALD was extracted through the failing heart and that transcardiac extraction of ALD correlated with LV end-diastolic volume index (LVEDVI) in patients with congestive heart failure, the existence and increase of ALD synthase in the hearts of infarct rats were reported, suggesting cardiac production of ALD in patients with AMI. METHODS: We measured plasma ALD in the aortic root (Ao) and coronary sinus (CS) in 57 consecutive patients who received successful revascularization and enalapril, with first AMI at acute phase and after one month. We also measured plasma procollagen type III aminoterminal peptide (PIIINP) in the CS. RESULTS: Plasma ALD was significantly lower in the CS than it was in the Ao at the acute phase (84.7 +/- 6.3 pg/ml vs. 105.5 +/- 8.0 pg/ml, p < 0.0001). Significant positive correlations exist between the transcardiac gradient of ALD at the acute phase and the LVEDVI at one month. Moreover, the transcardiac gradient of plasma ALD at the acute phase has a significant correlation with plasma PIIINP, a biochemical marker of fibrosis, after one month. Stepwise multivariate analysis showed that transcardiac extraction of plasma ALD at the acute phase had an independent and significant positive relationship with a large LVEDVI after one month. CONCLUSIONS: These results indicate that plasma ALD is extracted through the heart in patients with AMI at the acute phase and that the extracted ALD plays an important role in modulating post-infarct LV remodeling.
Acute Disease↗