Value of 3D CTA in association with accessory anterior cerebral artery with ruptured anterior communicating artery aneurysm.
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Aged↗
Biomedical subjects
N Aoyama
Publications and source records attributed to N Aoyama.
Dedifferentiation and decreased expression of adhesion molecules, E-cadherin and ZO-1, in colorectal cancer are closely related to liver metastasis.
Carcinoma cells with high metastatic potential often show a dedifferentiated phenotype at the primary site. In this study, a total of 48 cases (24 primary tumors of colorectal cancer (Pr-CRC) with liver metastasis, 24 without) were examined for E-cadherin and ZO-1 expression by immunohistochemical staining, and for their dedifferentiated phenotype. The expression levels of E-cadherin and ZO-1 were markedly decreased in the cancer cells of tumors with liver metastasis. Moreover, dedifferentiation of cancer cells, which was evaluated by the modified Gleason score, was also related to liver metastasis. However, none of the conventional clinicopathologic parameters of invasion, except lymph node metastasis, showed any relationship with liver metastasis. These results indicate that dedifferentiation and a decreased expression of E-cadherin and ZO-1 are closely related to liver metastasis.
Cadherins↗
Mechanisms of the mass effect of cerebral contusion: ICP monitoring and diffusion MRI study.
OBJECTIVE: Cerebral contusion is sometimes associated with a non-hemorrhagic mass effect which progresses rapidly within 12-48 hours post-trauma. In order to determine the mechanisms underlying such a mass effect, we analyzed data obtained from ICP monitoring and diffusion MRI in a total of 38 patients with cerebral contusion. METHODS: Diffusion imaging and ADC mapping were performed employing 1.5 T echo planar MRI. ADC values were expressed as a ratio relative to the values of intact brain areas. RESULTS: In 6 patients, ICP became uncontrollable medically and surgical resection of the contused brain tissue was eventually performed. Within 24 hours post-trauma, diffusion images revealed a low intensity core and a high intensity rim in the contusion. The ADC ratio increased in the central area (1.13 +/- 0.21) and decreased in the peripheral area (0.67 +/- 0.14). A crescent-shaped zone of very high ADC ratio (1.45 +/- 0.14) was observed at the border between these two areas during the period of 24-48 hours. CONCLUSIONS: It appears that the capacitance of edema fluid accumulation is elevated by cellular disintegration in the central area, whereas the resistance to edema fluid propagation is elevated by cellular swelling in the peripheral area. We suggest that such events facilitate extracellular edema fluid accumulation within contused brain tissue and contribute, together with cellular swelling itself, to the non-hemorrhagic mass effect of cerebral contusion.
Brain Concussion↗
Variation in MT expression in early-stage depressed-type and polypoid-type colorectal tumours.
Metallothionein (MT) expression is observed in various carcinomas, but its role is not fully understood. To clarify the clinicopathological significance of MT, 87 colorectal adenomas and 128 early-stage carcinomas were immunohistochemically analysed for MT expression. The degree of MT immunostaining of a specimen was graded according to the proportion of MT-positive cells; negative (<5%) and positive (focally 5-50%, diffusely >50%). MT expression significantly decreased with tumour development. For carcinomas, MT-positivity was significantly associated with depth of invasion (T1 60% versus T2 33%; P<0.01), vascular involvement (positive 35% versus negative 61%; P<0.01) and morphology (polypoid 62% versus depressed 26%; P<0.01). Regarding MT-positive distribution, the diffuse-positive rate in MT-positive polypoid lesions was 28%, while MT-positive depressed lesions were all diffusely stained (P<0.01). In conclusion, our results suggested that decreasing MT expression is an early event in colorectal carcinogenesis and may reflect local invasion. Furthermore, MT-positive distribution may reflect genetic differences between the polypoid and depressed-type.
Adult↗
Early and long-term results of coronary artery bypass grafting in dialysis patients.
OBJECTIVE: We evaluated the surgical outcome of coronary artery bypass grafting in dialysis patients. METHODS: We retrospectively analyzed 25 consecutive dialysis patients requiring isolated coronary artery bypass grafting. Their mean age was 61.6 years and average dialysis duration 80.4 months. RESULTS: Eight patients (32%) had emergency or urgent surgery. The mean number of bypassed vessels was 3.3 +/- 1.2. Internal thoracic artery grafts were used in 19 patients and gastroepiploic artery grafts in 5. Two (8%) died during hospitalization and complications occurred in 11 (44%). No cerebral complications were observed. All survivors showed ameliorated symptoms and improved overall function. Of 14 late deaths, 5 were cardiac-related, with 2 involving obvious myocardial ischemic events. Actuarial survival, including hospital deaths, at 1 year was 70.9%, at 3 years was 43.5%, and at 5 years was 34.8%. Cardiac-death-free survival was 70.2% at 3 years and 70.2% at 5 years. CONCLUSION: Coronary artery bypass grafting in dialysis patients is associated with a higher incidence of complications but has acceptable surgical mortality and effectively relieves angina symptoms.
Aged↗
Prognosis of patients with advanced carcinoma of the esophagus with complete response to chemotherapy and/or radiation therapy: a questionnaire survey in Japan.
BACKGROUND: We estimated the survival of patients with advanced carcinoma of the esophagus in Japan who achieved complete response (CR) with chemotherapy and/or radiation therapy. METHODS: A questionnaire was designed for patients with cancer of the esophagus with pretreatment stage II-IV (excluding organ metastasis [M1]), who were treated with chemotherapy and/or radiation therapy and achieved either a clinical CR continuing for more than 1 year, or a pathological CR in surgical specimens. All patients were treated between January 1, 1990, and December 31, 1997, in Japan. RESULTS: Of the 169 eligible patients for whom adequate data were available, 106 patients with continuing clinical CR were defined as group A and 63 with pathological CR as group B. The overall survival rates at 5 years were 62.4% in group A and 64.8% in group B. In each of groups A and B, there was no significant difference in overall survival among subgroups of patients classified by initial pretreatment clinical stage. In group A, the survival rate of patients with concurrent chemotherapy and radiation therapy was significantly better than the rates for patients with chemotherapy alone or radiotherapy alone. In group A, the frequency of first failure at the local site of esophageal carcinoma was 7.7%. Of the 12 patients in group B (19%) who died less than 1 year postoperatively, 6 died of postoperative complications. CONCLUSION: The effect of CR to chemotherapy and/or radiation therapy for carcinoma of the esophagus on survival was marked. In patients with esophageal carcinoma who achieve CR, the prognosis may be independent of the initial pretreatment stage. Local failure in group A patients remains a problem, however.
Adult↗
Glut1 expression in T1 and T2 stage colorectal carcinomas: its relationship to clinicopathological features.
Glucose uptake is mediated by glucose transporter (Glut) proteins, which exhibit altered expression in a variety of malignant neoplasms. Glut1 expression is thought to be a potential marker for malignant transformation. The aim of the present study was to investigate the expression of Glut1 protein in colorectal adenomas, T1 and T2 stage carcinomas. Immunohistochemical detection of Glut1 protein was examined in 141 formalin-fixed and paraffin-embedded colorectal tumour specimens (57 adenomas, 84 carcinomas). The degree of Glut1 immunostaining of a specimen was graded according to the proportion of Glut1-positive cells in it; absent (positive cells are 0%), weakly positive (less than 10%), moderately positive (10-50%), and strongly positive (more than 50%). Glut1 expression was present in 18% of the adenomas with low-grade dysplasia, and in 63% of the adenomas with high-grade dysplasia. The positivity in such lesions was usually weak, but was moderate in 8% of the adenomas with high grade dysplasia. For the carcinomas, there were significant correlations between Glut1-positivity and depth of invasion (T1 45% versus T2 74%, P<0.01), histological differentiation (well 49% versus moderately to poorly 74%, P< 0.05) and morphological type (polypoid 42% versus depressed 73%, P< 0.05), if the cut-off value was set at 10% of cells. In conclusion, we clarified the relationship between Glut1 expression and clinicopathological features in T1 and T2 stage colorectal carcinomas, and our results suggested a high malignant potential of the depressed-type carcinoma.
Adenocarcinoma↗
CYP2C19 genotype related effect of omeprazole on intragastric pH and antimicrobial stability.
PURPOSE: A combination of proton pump inhibitors and antimicrobials has been applied as an anti-Helicobacter pylori (H. pylori) therapy. Omeprazole, one of the proton pump inhibitors, is metabolized by CYP2C19. which exhibits genetic polymorphism. It was reported previously that the overall anti-H. pylori efficacy can be related to the CYP2C19 genotype. The main aim of the present study was to obtain a rational explanation for the relationship between the overall anti-H. pylori efficacy and the CYP2C19 genotype. METHODS: Six healthy volunteers were classified as extensive metabolizers and poor metabolizers, according to their CYP2C19 genotypes. Plasma concentrations and intragastric pH were monitored prior to and until 24 h after the administration of 20 mg omeprazole. The stability of amoxicillin, clarithromycin, and metronidazole was examined using buffer solutions with monitored intragastric pH, and their remaining percentage in the intragastric space was simulated. RESULTS: The poor metabolizers, classified by the CYP2C19 genotypes, showed the higher effectiveness in anti-H. pylori therapy, via the higher plasma concentration of omeprazole and the higher intragastric pH, and possibly the higher stability of antimicrobials in the higher intragastric pH. CONCLUSIONS: CYP2C19 genotyping is a very useful method to determine the effective and safe dosage regimen including the selection of the dual and triple therapy in anti-H. pylori therapy.
Amoxicillin↗
CYP2C19 genotype and pharmacokinetics of three proton pump inhibitors in healthy subjects.
PURPOSE: To predict the CYP2C19 genotype-dependence in anti-Helicobacter pylori (H. pylori) therapy when lansoprazole or rabeprazole was used instead of omeprazole as a proton pump inhibitor (PPI). METHODS: A comparative pharmacokinetic study with each PPI was designed as an open, randomized, and crossover study of 18 Japanese healthy volunteers who were classified into the homozygous, heterozygous extensive metabolizer and the poor metabolizer based on the CYP2C19 genotype determined by PCR-RFLP method. Each subject received a single oral dose of 20 mg omeprazole, 30 mg lansoprazole, or 20 mg sodium rabeprazole, with at least 1 week washout period between treatments. Plasma concentrations of PPIs and their metabolites were monitored until 12 h after medication. RESULTS: Pharmacokinetic profiles of omeprazole and lansoprazole were well correlated with the CYP2C19 genotype. The heterozygous extensive metabolizer was slightly different from the homozygote, but there was no statistically significant difference. The CYP2C19 genotype dependence found for lansoprazole was not obvious compared with omeprazole. As for rabeprazole, the pharmacokinetic profile was independent of the CYP2C19 genotype. CONCLUSIONS: CYP2C19 genotype dependence will be found in the anti-H. pylori therapy even when lansoprazole is used as the PPI.
2-Pyridinylmethylsulfinylbenzimidazoles↗
MDR1 genotype-related pharmacokinetics of digoxin after single oral administration in healthy Japanese subjects.
PURPOSE: To evaluate the MDR1 genotype frequency in the Japanese population and to study the relationship between the MDR1 genotype and the pharmacokinetics of digoxin after single oral administration in healthy subjects. METHODS: The MDR1 genotype at exon 26 was determined in 114 healthy volunteers by polymerase chain reaction-restriction fragment length polymorphism. The serum concentration-time profile of digoxin was examined after single oral administration at a dose of 0.25 mg. RESULTS: It was found that 35.1 % (40/114) of subjects were homozygous for the wild-type allele (C/C). 52.6% (60/114) were compound heterozygotes with a mutant T-allele (C3435T) (C/T), and 12.3% (14/114) were homozygous for the mutant allele (T/T). There was no effect of gender or age on the distribution. The serum concentration of digoxin after a single oral administration increased rapidly, attaining a steady state in all subjects; however, it was lower in the subjects harboring the T-allele. AUC0-4 h values (+/-SD) were 4.11 +/- 0.57, 3.20 +/- 0.49. and 3.27 +/- 0.58 ng h/ml, respectively, with a significant difference between C/C and C/T or T/T. CONCLUSIONS: The serum concentration of digoxin after single oral administration was lower in the subjects harboring a mutant allele (C3435T) at exon 26 of the MDR1 gene.
Adult↗
Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).
BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.
Adult↗
N-Acetyltransferase 2 genotype correlates with sulfasalazine pharmacokinetics after multiple dosing in healthy Japanese subjects.
Sulfapyridine (SP) is metabolized by polymorphic N-acetyltransferase 2 (NAT2) [EC 2.3.1.5]. In this study, the correlation between the NAT2 genotype and the pharmacokinetics of SP after multiple oral dosing of sulfasalazine (SASP) was examined to elucidate the effect of multiple dosing on the predictability of the phenotype by NAT2 genotyping. Seven healthy subjects were classified into two groups; the homozygotes for the wild-type allele, NAT2*4/*4 (Group I) and the compound heterozygotes for the mutant allele (NAT2*4/*6A or NAT2*4/*7B) (Group II). All received once-daily 1 g of SASP (Salazopyrin) orally for 8 d. Plasma concentrations and urinary recoveries of SASP, SP and N-acetylsulfapyridine (AcSP) were monitored for 8 d. At 24 h on Day 1, the plasma concentration of SASP was lower and those of SP and AcSP were higher in Group II compared with Group I, but there was no significant difference. The plasma concentration ratio of AcSP to SP (AcSP/SP) tended to be lower in Group II. Urinary recoveries of SP and AcSP were increased in Group II, and their ratio was slightly reduced in Group II. Multiple dosing for 8 d resulted in an increase in the plasma concentrations of SASP, SP and AcSP. The difference between Group I and II was marked compared with single dosing, resulting in a significant difference in the plasma concentration of SP and the ratio of AcSP/SP. The simple input-output pharmacokinetic model applied for the analysis of plasma concentrations and urinary recoveries of SP and AcSP suggested the acetylation of SP into AcSP was 2.7-fold reduced in Group II (p=0.064).
Acetylation↗
A peptide fragment of beta cardiac myosin heavy chain (beta-CMHC) can provoke autoimmune myocarditis as well as the corresponding alpha cardiac myosin heavy chain (alpha-CMHC) fragment.
The validity of the general belief that alpha cardiac myosin heavy chain (alpha-CMHC) is primarily responsible for causing experimental autoimmune myocarditis because of the more profound tolerance induction to beta-CMHC due to its expression during the embryonic stage has been examined. In order to completely avoid cross-contamination among components of the two myosin heavy chains, recombinant myosin fragments were synthesized in Escherichia coli using cDNA fragments of rat alpha- and beta-CMHC cloned by reverse transcription polymerase chain reaction (RT-PCR). Two fragments corresponding to amino acid residues 1107-1164 derived from alpha- and beta-heavy chains were equally capable of provoking severe myocarditis in Lewis rats when immunized in complete Freund's adjuvant. No significant differences in the severity, as judged from histological scoring, were observed between the diseases induced by the two different peptide fragments, indicating conclusively that beta-CMHC is as pathogenic as alpha-CMHC.
Amino Acid Sequence↗
[Rapid urease test].
The rapid urease test is a simple, sensitive, and highly specific test that enables the endoscopist to diagnose Helicobacter pylori infection in the endoscopy room. Determination of the infection status of Helicobacter pylori by biopsies from the gastric body had a significantly higher sensitivity than antral biopsies. A false-negative reaction by rapid urease test occurred the use of antibiotics (correlates with clearance of the bacteria) and the use of proton pump inhibitor or a part of mucosal protective agents(correlates urease inhibitory effect) and in the case of non-urease producing Helicobacter pylori. The rapid urease test satisfactory overall sensitivity before eradication treatment. However, the sensitivity of these rapid urease tests was lower after eradication than before eradication.
Clinical Enzyme Tests↗
Heterogeneous mechanisms of early edema formation in cerebral contusion: diffusion MRI and ADC mapping study.
Severe cerebral contusion is sometimes associated with early edema formation within 24-48 hours post-trauma, and this frequently results in progressive ICP elevation and clinical deterioration. To investigate the underlying mechanisms of such severe contusion edema, diffusion imaging and ADC mapping were performed in 20 patients with cerebral contusion, employing 1.5 T echo planar MRI. Within 24 hours post-trauma, the diffusion images demonstrated a low intensity core in the central area and a high intensity rim in the peripheral area of contusion. The ADC value increased in the central area (ADC ratio (contusion/normal brain) = 1.13 +/- 0.13) and decreased in the peripheral area (ADC ratio = 0.83 +/- 0.13). This suggested that intra- and extracellular components underwent disintegration and homogenization within the central area, whereas cellular swelling was predominant in the peripheral area. A crescent-shaped zone of very high ADC value (ADC ratio = 1.38-1.61) was observed at the border between these two areas during the period of 24-48 hours post-trauma in some cases, apparently indicating that edema fluid was accumulated within a space formed by homogenization. The ADC values in the peripheral area shifted to an increase after 48-72 hours post-trauma. These findings imply that multiple mechanisms operate in early edema formation in cerebral contusion. It appears that the capacity for edema fluid accumulation increases in the central area and resistance for edema fluid propagation is elevated by cellular swelling in the peripheral area. We suggest that a combination of such events facilitates edema fluid accumulation in the central area and contributes, together with the cellular swelling in the peripheral area, to the mass effect of contusion edema. Diffusion MRI and ADC mapping represent powerful tools for investigating spatially as well as temporally heterogeneous mechanisms of contusion edema.
Brain↗
Flat-elevated and depressed, subtypes of flat early colorectal cancers, should be distinguished by their pathological features.
Flat-type colorectal tumors have are being detected with increasing frequency. It has become clear that these flat lesions contain two subtypes; flat-elevated and depressed lesions. However, their clinicopathological features and roles in colorectal carcinogenesis remain obscure. We classified colorectal adenomas and submucosal invasive cancers into three types: polypoid, flat-elevated, and depressed types. A clinicopathological study of 2505 colorectal tumors (2407 adenomas, 98 submucosal invasive cancers) was then performed. Furthermore, 64 tumors (25 adenomas with high-grade dysplasia, 39 submucosal invasive cancers) from which DNA was extracted were examined for K-ras gene mutation. The percentages of each configuration in the resected materials were 62.0%, 36.4%, and 1.6% of the polypoid, flat-elevated, and depressed types, respectively. The rate of submucosal invasive cancer in the depressed type was always high regardless of size. In the polypoid and flat-elevated types, lesions of larger size showed higher rates of invasion. Analysis of submucosal invasive cancers revealed no adenomatous components in any of the depressed-type lesions; in the polypoid and flat-elevated types the frequencies of cancer with adenomatous components were 83.6% and 77.8%, respectively. The flat-elevated type was more frequently located (77.8%) in the proximal colon than the other types (polypoid type 16.4%, depressed type 25.0%). The incidence of K-ras gene mutation was 47.2%, 18.2%, and 0% in the polypoid, flat-elevated, and depressed types, respectively. These findings suggest that the flat-elevated and depressed types are similar in that they are both morphologically flat and have infrequent incidences of K-ras gene mutation, but these two lesions differ in their pathological features. Especially, depressed type lesions have a tendency to invade the submucosal layer even when they are small. Therefore one should always be aware of this type of lesion during colonoscopic examination.
Adenoma↗
Laparoscopic lower anterior resection is equivalent to laparotomy for lower rectal cancer at the distal line of resection.
BACKGROUND: Procedures that involve resection of the distal rectum challenge the current limitations of laparoscopic technology, because of lack of compact articulating stapling instruments. METHOD: We improve the procedure with the aid of a Lap disk, an abdominal wall sealing device that was developed for hand-assisted manipulation. A linear stapler capable of changing its stop angle is inserted through the disk, and the rectum is transected by the disk during a second pneumoperitoneum. RESULTS: The transection line becomes equivalent to that obtained with laparotomy. CONCLUSION: This new technique made laparoscopic lower anterior resection possible to transect the lower rectum in the same way as is done with laparotomy.
Abdominal Muscles↗
Analysis of Helicobacter pylori vacA gene and serum antibodies to VacA in Japan.
Vacuolating cytotoxin, VacA, is one of the most important pathogenetic factors produced by Helicobacter pylori. However, it is not clear whether the diversity in disease outcome may be ascribed to variations in strain and/or to the host responses to virulence factors. In this study, we analyzed the vacA middle region sequence among 65 Japanese isolates to clarify the variation in strain and assayed antibody titer to VacA by ELISA using purified VacA to evaluate the host response to cytotoxin. The nucleotide sequence identities compared among Japanese isolates were 92.8 +/- 3.56%, and compared to 88.3 +/- 2.89% in tox+ strains reported in GenBank. Positive correlation was found between the antibody titers and the severity of atrophic change of the stomach. In Japan the nucleotide sequences of the vacA middle region were highly homologous and genetically closer to tox+ strains. Antibody titers and host response to cytotoxin may be associated with atrophy of the stomach.
Adult↗