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Biomedical subjects

Eiji Uchida

Publications and source records attributed to Eiji Uchida.

At least 19 recordsLinked to original sources

Antitumor effect induced by dendritic cell (DC)-based immunotherapy against peritoneal dissemination of the hamster pancreatic cancer.

Establishing a method to control peritoneal dissemination is one of the most pressing issues in the postsurgical treatment of pancreatic cancer. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on peritoneal disseminations of hamster pancreatic cancer cells, PGHAM-1. After the orthotopically inoculation of 2 x 10(6) PGHAM-1 cells, DC pulsed with PGHAM-1-derived tumor lysates, DC alone or PBS as a vehicle was injected intraperitoneally (i.p.) three times at weekly intervals. The group treated with DC or DC+lysate was found to have smaller disseminated tumors than the vehicle-treated. In addition, mean survival time in the DC+lysate groups was significantly longer than the PBS group. These findings suggested that DC-based immunotherapy might be efficient for the treatment of peritoneal disseminations of the pancreatic cancer.

Animals↗

Adeno-associated viral vector-mediated expression of endostatin inhibits tumor growth and metastasis in an orthotropic pancreatic cancer model in hamsters.

We examined the feasibility of using adeno-associated virus (AAV)-mediated systemic delivery of endostatin in gene therapy to treat metastasis of pancreatic cancer. We established an animal model of orthotopic metastatic pancreatic cancer in which the pancreatic cancer cell line PGHAM-1 was inoculated into the pancreas of Syrian golden hamsters. Transplanted cells proliferated rapidly and metastasized to the liver. An AAV vector expressing endostatin (5 x 10(10) particles) was injected intramuscularly into the left quadriceps or intravenously into the portal vein. These routes of vector administration were evaluated by comparing various parameters of tumor development. Intramuscular injection of the vector modestly increased the serum endostatin level. The numbers of metastases and the incidence of hemorrhagic ascites were decreased in the treated animals. In contrast, the serum concentration of endostatin was significantly increased after intraportal injection of the vector. The antitumor effects on all parameters (including the size and microvessel density of primary pancreatic tumors, the sizes and number of liver metastases, and the incidence of hemorrhagic ascites) were significant. These results suggest that systemic delivery of endostatin represents a potentially effective treatment for pancreatic cancer and liver metastases. The route of vector administration influences the efficacy of AAV-mediated endostatin expression. Intraportal injection of the AAV vector appears to be more effective as an antiangiogenic gene therapy for pancreatic cancer.

Adenoviridae↗

The decrease of plaque volume during percutaneous coronary intervention has a negative impact on coronary flow in acute myocardial infarction: a major role of percutaneous coronary intervention-induced embolization.

OBJECTIVES: The aim of this study was to evaluate how decreased plaque volume during percutaneous coronary intervention (PCI) affects coronary flow in patients with acute myocardial infarction (AMI). BACKGROUND: Coronary flow after reperfusion therapy is a major determinant of clinical outcomes in patients with AMI. However, little is still known about the changes in coronary flow that appear after PCI in response to the decreased plaque during the procedure. METHODS: The study group comprised 60 patients with AMI who underwent pre- and post-PCI intravascular ultrasound (IVUS). Qualitative and quantitative analyses were performed on all IVUS procedures. External elastic membrane volume (EEMV), lumen volume (LV), and plaque volume (PV) were measured every 1.0 mm to include the lesion and reference segments 3.0 mm proximal and distal to the lesion. The difference between pre- and post-PCI PV was defined as the index of the decrease in plaque volume (DeltaPV). The corrected TIMI frame count (CTFC) was used to evaluate coronary flow after PCI. RESULTS: Plaque volume was decreased at post-PCI IVUS in all 60 patients. Inadequate reflow (CTFC >40) was observed in 13 patients (21.7%). The decrease in PV was significantly larger in patients with inadequate reflow than in those with reflow (49.4 +/- 18.9 vs. 31.7 +/- 15.5 mm(3), p = 0.0010). Also, DeltaPV was significantly correlated with CTFC after PCI (r = 0.415, p = 0.0012). CONCLUSIONS: The decrease in PV during PCI has a negative impact on coronary flow after PCI in patients with AMI. Embolization induced by PCI may occur in all patients with AMI.

Angioplasty, Balloon, Coronary↗

Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese.

AIMS: To investigate the effects of repeated grapefruit juice (GFJ) intake on the pharmacokinetics of atorvastatin and pravastatin in Japanese subjects. METHODS: Two randomized, two-way crossover studies were performed. GFJ or water was given to two groups of 10 subjects each three times daily for 2 days. On the third day, single 10 mg doses of atorvastatin or pravastatin were orally administered with GFJ or water, and an additional 250 ml of GFJ or water was taken before lunch and dinner. Plasma concentrations of atorvastatin and its metabolites were determined over 48 h postdosing and of pravastatin and its metabolites over 24 h postdosing. RESULTS: Compared with in the water group, the AUC(0,48 h) of atorvastatin acid significantly increased by 1.40 fold (95% CI 1.02, 1.92; P < 0.05) when atorvastatin was taken with GFJ. AUC(0,48 h) and C(max) of atorvastatin lactone significantly increased by 1.56 (95% CI 1.33, 1.83; P < 0.001) and 1.29 fold (95% CI 1.09, 1.51; P < 0.01), respectively, when atorvastatin was taken with GFJ. No significant changes were detected in any pravastatin pharmacokinetic parameter examined when pravastatin was taken with GFJ. However, AUC(0,24 h) of pravastatin lactone increased 1.31 fold (95% CI 1.01, 1.71; P < 0.05) with GFJ intake. CONCLUSIONS: GFJ was confirmed to significantly affect the pharmacokinetics of atorvastatin but had little or no effect on those of pravastatin in Japanese subjects.

Adult↗

The calcimimetic agent KRN 1493 lowers plasma parathyroid hormone and ionized calcium concentrations in patients with chronic renal failure on haemodialysis both on the day of haemodialysis and on the day without haemodialysis.

AIMS: Treatment with vitamin D sterols can lower plasma parathyroid hormone (PTH) in patients with secondary hyperparathyroidism; however, hypercalcaemia, hyperphosphataemia, or both, often develop. Calcimimetic agents, employed in alternative therapeutic approaches, directly inhibit PTH secretion by activating the calcium-sensing receptor in the parathyroid glands. METHODS: In this study, patients were given orally 25, 50, and 100 mg doses of the calcimimetic agent KRN 1493 each on two occasions, on the day of haemodialysis and on the day without haemodialysis. RESULTS: In the pharmacokinetic results, because the clearance of KRN 1493 by haemodialysis was much smaller than the systemic clearance, the influence of haemodialysis was not remarkable. In the pharmacodynamic study, on both the days with or without haemodialysis, plasma PTH concentrations decreased in a dose-dependent manner. Serum calcium concentrations decreased in association with the decrease in plasma PTH concentrations. Mild dose-dependent adverse effects (mainly nausea) were seen after the administration of KRN 1493 on both the day of haemodialysis and the day without haemodialysis. CONCLUSIONS: We conclude that the pharmacokinetics of KRN 1493 after a single administration were similar on the day of haemodialysis and the day without haemodialysis. KRN 1493 is safe and effective in suppressing PTH secretion and serum calcium concentrations on the day of haemodialysis and on the day without haemodialysis in patients with secondary hyperparathyroidism.

Administration, Oral↗

Convalescent stage coronary flow reserve and late myocardial morphologic outcomes in patients with first anterior acute myocardial infarction.

BACKGROUND: Microvascular damage immediately after reperfusion therapy is an independent predictor of left ventricular function in patients with acute myocardial infarction (AMI). However, its recovery may vary among individuals and the relationship between convalescent stage microvasculature and late myocardial morphologic change is unclear. METHODS AND RESULTS: Patients treated with coronary angioplasty within 12 h of their first anterior AMI were enrolled in this study. Coronary flow reserve (CFR) was measured 3 weeks post AMI, in both branches of the left coronary artery: culprit (left anterior descending artery: LAD) and non-culprit (left circumflex artery: LCX). Left ventriculography was performed at 3 weeks and 6 months post AMI and compared. Seventeen patients showed abnormal CFR in the LAD (Group 1: CFR<2), whereas 20 patients showed normal CFR (Group 2: CFR >/=2). Percent changes of end-diastolic volume tended to be higher in Group 1 than in Group 2 (11.8+/-21.6% vs -1.3+/-14.4%, p=0.056), and %changes of end-systolic volume was significantly smaller in Group 2 (11.8+/-22.1% vs -8.7+/-25.1%, p<0.05). A statistically significant correlation was found between absolute and relative CFR in the LAD and %change of end-systolic volume (r=-0.58: p<0.001, and r=0.40: p<0.05, respectively). CONCLUSIONS: Microvascular function in the convalescent stage may be related to these favorable changes.

Aged↗

A case report of duodenal carcinoid tumor associated with early gastric cancer.

A rare case of carcinoid tumor in the duodenal bulb associated with early gastric carcinoma is reported. An 85-year-old asymptomatic male was admitted to our hospital, referred by his neighboring doctor because of early gastric carcinoma shown by endoscopic examination. X-ray studies of the upper gastrointestinal tract showed irregular lesser curvature of the gastric antrum and a filling defect (phi1 cm) at the duodenal bulb. Gastric biopsy revealed the histological findings of Group V. Distal gastrectomy including the duodenal bulb with D2 lymph node dissection was performed. A resected specimens showed superficial depressed type carcinoma at the lesser curvature of the antrum, and an isolated submucosal tumor of 7x7 mm in size at the duodenal bulb. Histological examination disclosed papillary adenocarcinoma in the gastric mucosa and a carcinoid tumor of the duodenal bulb in the submucosal layer without high malignant findings. The patient has been well for 5 years since the surgery. In conclusion, we discussed 46 collected cases of carcinoid tumor of the duodenum associated with gastric carcinoma in Japan. Preoperative diagnosis of carcinoid tumor of the duodenum is very difficult, and thorough examinations are needed for submucosal lesion.

Adenocarcinoma, Papillary↗

Implementation of the diagnosis procedure combination in specific-function hospitals.

A Nobel medical payment system, the Diagnosis Procedure Combination (DPC), was implemented in Nippon Medical School Hospital and 81 other specific-function hospitals in 2003. This payment system depends on the length of hospital stay and diagnosis and medical procedures, and differs from the existing payment system, which depends on a piece rate. The daily payment differs for among almost 2,500 groups of DPC defined by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), and procedures, such as operations (K and J codes of the existing payment system). One of the most important outcomes may be a decrease in lengths of hospital stay, because the range of mean lengths of stay in specific-function hospitals has been officially stated to be 14 to 30 days, and the difference between the longest and shortest mean is almost double. The new medical payment system should stimulate competition among hospitals. In order to decrease the length of stay, we developed clinical pathways for patients undergoing surgery, such as laparoscopic cholecystectomy, gastrectomy, and inguinal hernia operations, as well as clinical protocols for the surgical procedures, such as percutaneous transhepatic cholangiodrainage (PTCD) and percutaneous endoscopic gastrostomy (PEG). Health care is undergoing a challenging transition, and we must improve patient care and clinical practice.

Critical Pathways↗

Simple closure of a perforated duodenal diverticulum: "a case report".

Spontaneous perforation of a duodenal diverticulum is a rare but serious complication with significant mortality rates. Just over 100 cases have been reported in the world literature. One case of perforated duodenal diverticulum treated by simple closure is reported. An elderly female was admitted to our hospital with an acute abdomen. Computed tomography of the abdomen showed retroperitoneal air around the duodenum and right kidney. Laparotomy with a Kocher maneuver disclosed a perforated diverticulum in the second portion of the duodenum. Although diverticulectomy is the most common treatment, simple closure of the perforated duodenal diverticulum with drainage was performed to avoid injury to the distal common bile duct and ampulla of Vater, which were close to the diverticulum. The patient has fully recovered and has been asymptomatic with no signs of recurrence for 25 months.

Aged↗

Decreases in serum apolipoprotein C-III concentration in cows with ethionine-induced fatty liver.

To monitor the serum concentration of apolipoprotein C-III (apoC-III), one of the functional apoproteins in lipid metabolism, in cows with ethionine-induced fatty liver, and to investigate the association of apoC-III with liver triglyceride (TG) content and serum biochemical variables, seven nonpregnant nonlactating Holstein cows (3 to 6 years old) were used. Five cows were treated with ethionine, an analogue of methionine, (days 0, 7 and 14). The remaining two controls received saline as the vehicle. Liver TG contents in the treated cows were increased markedly whenever administered, and significant increases were observed at days 14 (666.4%, 85.3 mg/g) and 21 (675.0%, 86.4 mg/g) compared with day 0. In controls, no significant changes in liver TG content and serum biochemical variables were observed during this experiment. The serum apoC-III concentration in the treated cows was decreased drastically after the first administration and fell to the lowest value at day 10 (76.2 microg/ml, 32% of day 0). The apoC-III was significantly (p<0.05) correlated with non-esterified fatty acids (r= -0.526), gamma-glutamyl transpeptidase (r= -0.407), total bilirubin (r= -0.464), positively with apolipoprotein B-100 (apoB-100, r=0.601) and cholesterol ester (r=0.449). Although apoB-100 concentrations were also reduced by the administrations, the concentrations tended to recover smoothly toward the next administration. The distinct difference in change between apoC-III and apoB-100 suggests that apoC-III may be regulated by other pathways, in addition to inhibiting the synthesis of apoproteins by ethionine.

Analysis of Variance↗

Tumor marker measurements of cells in a fine needle used for aspiration cytology.

OBJECTIVE: To investigate whether the needle washing could yield sufficient cells for tumor marker (TM) measurements as an ancillary technique to ensure the accuracy of fine needle aspiration cytology (FNAC) of tumors. STUDY DESIGN: After obtaining preliminary data that aspirated tumor cells within a 22-gauge needle could be collected by washing it with distilled water for TM measurements, we studied tumor cell numbers and TM values obtained by washing a 22-gauge needle directly after tumor aspiration and another needle after FNAC. RESULTS: Using 8 resected hepatobiliary and pancreatic carcinomas, the used needles yielded 16.8+/-10.5 x 10(4) cells per milliliter. Used needles from 6 adenocarcinomas expelled 479.2+/-406.5 ng/mL of carcinoembryonic antigen, and 6,561.3+/-5,713.1 ng/mL of CA 19-9, while the needles from 2 hepatomas showed normal values of those markers. CONCLUSION: A needle used for FNAC contains sufficient cells for TM measurements, which can be ancillary to the differential diagnosis.

Adenocarcinoma↗

One-step insertion of an expandable metallic stent for unresectable common bile duct carcinoma.

BACKGROUND: This report describes a one-step insertion of an expandable metallic stent to treat obstructive jaundice due to unresectable common bile duct carcinoma. METHODS: A percutaneous transhepatic cholangiogram is obtained, and the bile duct obstruction is negotiated with a guide wire. After advancing the catheter into the duodenum, contrast material is injected to measure the length of the stenosis. After an expandable metallic stent is positioned, an external biliary drainage catheter is left in place to provide temporary drainage. The catheter is removed after stent patency is confirmed after 3 days. CONCLUSIONS: One-step insertion of an expandable metallic stent for biliary obstruction is a useful method that shortens hospitalization. Once it has been decided to use stent palliation, the stent should be inserted without undue delay to maximize symptomatic relief and cost benefits.

Aged↗

Infected solitary hepatic cyst.

An unusual case involving an infected hepatic cyst in which the correct diagnosis was made without operation is reported. A 93-year-old woman presented with acute onset of right upper quadrant abdominal pain, mild left lower quadrant abdominal pain, diarrhea, and fever. On admission, computed tomography revealed a 15 cm solitary hepatic cyst in the anterior-superior segment of the liver with a thickened wall that enhanced with contrast media. Ultrasonography demonstrated a 15 cm anechoic lesion with a hypoechoic area in the dependent portion of the cyst and a thickened wall. The serum concentration of C-reactive protein was 24.3 mg/dL, and the white blood cell count was 13,800/microL. A diagnosis of infected hepatic cyst was suspected, and percutaneous transhepatic drainage of the cyst was performed. Milky yellow fluid was obtained and the patient's right upper quadrant abdominal pain resolved after drainage. Klebsiella pneumoniae was cultured from the drainage fluid. The patient was discharged 20 days after drainage. Infection has not recurred and the hepatic cyst has not enlarged after 18 months.

Aged↗

[Non-radioactive PCR southern method for analysis of CTG repeat in myotonic dystrophy].

Myotonic dystrophy (MyD) is a hereditary neuromuscular disorder of an autosomal dominant trait. MyD is caused by an expansion of unstable CTG trinucleotide repeat in the 3' untranslated region of mRNA coding myotonin protein kinase (MT-PK). We analyzed CTG repeat expansion in 10 patients with congenital MyD and their relatives using the non-radioactive PCR Southern method. The region containing the CTG repeat was amplified by PCR using specific primers. The PCR products were electrophoresed on a 1% agarose gel and transferred to a nylon membrane. The CTG repeat expansion was shown using a fluorescein-labelled (CTG) 10 probe. To estimate the number of CTG repeats, we compared the smears obtained on Southern blotting with a picture of PCR products and a DNA size marker (100 bp). We compared our results of radioactive Southern blotting for genomic DNA digested by Eco RI or Bgl I and for PCR products. In congenital MyD patients, heterogeneous smears (3.89-10.22 kb:about 1252-3362 CTG repeat) were observed, whereas in the adult type MyD had heterogeneous smears (0.92-1.82 kb:about 262-562 CTG repeat). In asymptomatic MyD patients, there were heterogeneous smears (0.35-1.16 kb:about 72-342 CTG repeat). These results demonstrated anticipation. We conclude that the non-radioactive PCR Southern method is useful and convenient for the DNA diagnosis of MyD.

Adult↗

Chlamydial infection in canine atherosclerotic lesions.

We attempted to detect chlamydial antigens in canine atherosclerotic lesions from seven dogs by immunohistochemical technique using anti-Chlamydia psittaci (C. psittaci) polyclonal and anti-C. pneumoniae monoclonal antibodies. Immunopositive signals to both antibodies were recognized in the atherosclerotic lesions of the aortas, coronary and splenic arteries of all dogs. Positive signals were found in the foamy cytoplasm of infiltrated macrophages and extracellular matrices in the lesions. In some lesions, cytoplasm of the endothelial cells and smooth muscle cells was also immunopositive against both antibodies. By electron microscopy, chlamydial microorganisms were found in the cytoplasm of endothelial cells and smooth muscle cells. Using polymerase chain reaction (PCR), detection of C. pneumoniae DNAs were performed in the spleen, heart (coronary arteries) and kidney in one of the seven dogs. Positive 314 bp PCR products were obtained in all samples of the dog. These results confirmed the presence of viable Chlamydiae in atheromas and supported the conclusion that the organism may be an active factor in the pathogenesis of canine, as well as human atherosclerosis.

Animals↗