Dutasteride-mediated morphological changes in the genitourinary tract associated with altered expression patterns of the androgen and estrogen receptors in male rats.

We evaluated the effects of dutasteride on the genitourinary tract using fifteen 8-week-old male Sprague-Dawley rats. Animals were divided into three groups comprising five animals each and treated as follows. Group A was a control group, members of Group B received oral administration of dutasteride 0.1 mg/kg/day from the age of 8 to 16 weeks, and members of Group C were castrated at the age of 8 weeks. All rats were killed at the age of 16 weeks for the sample collection of blood, bladder, prostate, seminal vesicles, and penis. Then, we evaluated the pathological examination for evaluating the tissue fibrosis and hormonal receptor expression. The results showed that the mean size of the prostate and seminal vesicles was smaller in Group B and Group C than in Group A. Serum and tissue concentrations of both testosterone and dihydrotestosterone were remarkably reduced in serum and all tissues in Group C compared with Group A. On the other hand, in Group B, only dihydrotestosterone was reduced in serum and penis. Histopathological examination revealed that Group C showed statistically significant histological changes, such as an increase in fibrotic tissue in the bladder, prostate, and penis. Similarly, Group B showed fibrotic changes in the prostate and penis compared with the Group A. Immunofluorescent staining revealed that the androgen receptor was more strongly expressed than the estrogen receptor beta in Group A. On the other hand, in Group C, weak expression of the androgen receptor and strong expression of the estrogen receptor beta was noted. In Group B, these changes were noted in the prostate and penis. These findings suggest that dutasteride cause morphological changes not only in prostate but also in penis. These changes are associated with altered expression patterns of androgen receptor and estrogen receptor.

Prospective assessment of health-related quality of life in men with late-onset hypogonadism who received testosterone replacement therapy.

The objective of this study was to characterise the status of health-related quality of life (HRQOL) in Japanese men with late-onset hypogonadism (LOH) treated with testosterone replacement therapy (TRT). HRQOL in 69 consecutive Japanese men with LOH undergoing TRT for at least 6 months was prospectively evaluated before and 6 months after the initiation of TRT using the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8). All eight-scale scores except for bodily pain (BP) in the 69 patients at 6 months after the introduction of TRT significantly improved compared with those before TRT; however, all scale scores except for BP in the 69 patients were significantly inferior to those in age-matched Japanese controls irrespective of the timing of SF-8. Multivariate analyses of several parameters revealed that both age and Aging Male Symptom (AMS) score had an independent impact on mental health (MH), despite the lack of an independent association between any score and the remaining factors examined. TRT appeared to significantly improve the status of HRQOL in men with LOH; however, even after the introduction of TRT, HRQOL associated with MH remained significantly impaired in elderly men and/or those with a high AMS score.

Effect of famotidine on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer.

AIM: We investigated the effect of acid suppression therapy on recurrent bleeding after successful endoscopic treatment of bleeding peptic ulcer. METHODS: A total of 400 patients with bleeding peptic ulcer received either intravenous infusion of famotidine (40 mg/day) (n = 207, 163 males, 44 females, mean age 61.5 years) or drip infusion of omeprazole (40 mg/day; n = 193, 134 males, 59 females, mean age 59.8 years) after successful endoscopic treatment. The fasting duration, hospital stay, volume of transfused blood, incidence of rebleeding and mortality were compared between the two groups. RESULTS: The incidence of rebleeding did not differ significantly between the famotidine group (9%) and the omeprazole group (8%). The mean hospital stay was significantly shorter in the omeprazole group (18.4 days) than in the famotidine group (21.5 days, P = 0.009). However, there was no statistically significant difference in fasting duration, volume of transfused blood or mortality. CONCLUSION: Our findings indicate that intravenous infusion of famotidine after successful endoscopic treatment is equivalent to drip infusion of omeprazole for prevention of recurrent bleeding.

Hyperinsulinemia as a risk factor for restenosis after coronary balloon angioplasty.

The present study evaluated whether hyperinsulinemia is a predictor of restenosis after coronary balloon angioplasty in 69 patients who underwent elective coronary balloon angioplasty; patients were excluded if they were known diabetics being treated with insulin. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Restenosis was defined as the presence of > or = 50% stenosis at follow-up. Plasma insulin responses before, 30, 60, and 120 min after 75 g glucose load (OGTT) were measured. Plasma insulin levels were higher in patients with restenosis than in patients without restenosis. Minimal lumen diameter at follow-up was smaller, and percent diameter stenosis at follow-up was higher and late loss was greater in the highest sum of insulin levels during OGTT (sigma insulin) quartile (0.95+/-0.15 vs 1.47+/-0.09 mm, p=0.005; 66.3+/-5.8 vs 40.5+/-3.3%, p=0.0003; 0.90+/-0.15 vs 0.49+/-0.08 mm, p=0.02). Even after adjustment for coronary risk factors and administration of angiotensin converting enzyme inhibitors, the association of hyperinsulinemia with restenosis leads to the conclusion that hyperinsulinemia is a strong risk factor for restenosis.

A low 13C-urea breath test value is associated with increased risk of gastric cancer.

PURPOSE: The 13C-urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Values are affected by H. pylori infection and by the severity of atrophic gastritis. Our objective was to determine the association of UBT values with gastric cancer, and to evaluate the risk of gastric cancer in terms of UBT values. METHODS: Our study involved 413 consecutive patients who had undergone esophagogastroduodenal examination and the UBT test. RESULTS: Of the 398 patients with positive UBT results, atrophy and intestinal metaplasia scores in both antrum and corpus were significantly higher in patients with gastric cancer than in those with gastritis, duodenal ulcer, and gastric ulcer. The UBT value related to gastric cancer (22.01 +/- 1.89%o) was significantly lower than that for gastritis (35.19 +/- 1.53%o; P < 0.01), duodenal ulcer (29.01 +/- 1.97%; P < 0.05), or gastric ulcer (30.79 +/- 2.83%; P < 0.05). When the UBT values were less than 20%, increases in the risk of gastric cancer correlated with decreasing UBT values. CONCLUSIONS; These findings indicate that the UBT value related to gastric cancer is significantly lower than that for gastritis, duodenal ulcer, or gastric ulcer in H. pylori-positive patients. Low UBT values were associated with the risk of gastric cancer.

Hyperinsulinemia for the development of hypertension: data from the Hawaii-Los Angeles-Hiroshima Study.

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.

Interleukin 8 and vascular endothelial growth factor -- prognostic factors in human gastric carcinomas?

Gastric carcinoma cells express potent angiogenic factors including vascular endothelial growth factor (VEGF). We previously reported that interleukin-8 (IL-8) acts as an angiogenic factor for human gastric carcinomas. More recently, we found that IL-8 upregulates matrix metalloproteinase-9 (MMP-9) expression and increases invasive activity of gastric carcinoma cells. The purpose of this study was to determine whether the expression of IL-8 and VEGF correlates with clinicopathological parameters in human gastric carcinomas. IL-8 and VEGF expression levels were measured by an enzyme-linked immunosorbent assay (ELISA) in 56 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumour findings, presence of metastasis and prognosis were obtained from the patient records and endoscopic, surgical and pathological reports. IL-8 protein levels were higher in most neoplasms than in the corresponding normal mucosal tissue. In contrast, VEGF expression in the tumours was similar to that in normal mucosa. The IL-8 level in the neoplasms correlated significantly with the depth of invasion, venous invasion and lymphatic invasion. VEGF expression in the tumours correlated well with the depth of invasion and lymph node metastasis. No correlation between IL-8 and VEGF expression in the tumours was observed. The survival rates of patients with tumours displaying high IL-8 and VEGF expression levels were significantly lower (P<0.05) than those of patients with tumours displaying low IL-8 and VEGF expression. The results suggest that IL-8 and VEGF may be independent and important prognostic factors in human gastric carcinomas.

Clinicopathological significance of vascular endothelial growth factor (VEGF)-C in human esophageal squamous cell carcinomas.

The purpose of this study was to investigate the expression of vascular endothelial growth factor (VEGF) -C in human esophageal squamous cell carcinomas to elucidate its role in lymph node metastasis and tumor progression. The expression of VEGF-C and flt-4 genes was examined in 5 esophageal carcinoma cell lines, 12 fresh biopsy specimens and 48 archival surgical specimens of human esophageal carcinoma tissues by RT-PCR and immunohistochemistry. Immunohistochemistry using antibodies against CD34 (endothelial cell specific) was also carried out and microvessels were quantified by counting vessels in a 200x field in the most vascular area of the tumor. Of the 5 human esophageal carcinoma cell lines, 4 constitutively expressed VEGF-C mRNA. In 8 (66.7%) of 12 cases, VEGF-C mRNA was detected in only tumor tissues but not in normal mucosa by RT-PCR. There was a significant relationship between VEGF-C and flt-4 mRNA expression. Out of the 48 surgical specimens of esophageal carcinomas, 19 (39.6%) and 10 (20.8%) exhibited intense VEGF-C immunoreactivity in the cytoplasm of many cancer cells and the stromal cells, respectively. In contrast, Flt-4 was mainly expressed on the lymphatic endothelial cells. Normal and dysplastic esophageal squamous epithelium exhibited no or faint cytoplasmic staining of VEGF-C. VEGF-C expression correlated with depth of tumor invasion, tumor stage, venous invasion, lymphatic invasion and lymph node metastasis. Vessel count was significantly higher in the VEGF-C positive tumors than in the negative tumors. These results overall suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and angiogenesis in human esophageal carcinoma.

Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: a comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component.

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.

Effects of omeprazole and pirenzepine on enterochromaffin-like cells and parietal cells in rat stomach.

PURPOSE: The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and pirenzepine. METHODS: The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined. RESULTS: Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and pirenzepine were between those produced by treatment with omeprazole alone and pirenzepine alone. CONCLUSIONS: Omeprazole-induced hypergastrinemia and pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells.

Protective effect of ammonia against reflux esophagitis in rats.

Although several recent studies have reported that curing Helicobacter pylori (H. pylori) may result in the development of reflux esophagitis (RE), the mechanisms leading to this complication are unknown. One by product of H. pylori infection is ammonia, which serves as an acid neutralizer. The aim of this study was to clarify whether ammonia, which is produced during H. pylori infection, has a protective effect on the esophagus. Eight-week-old male Sprague-Dawley rats were fasted for 24 hrs. Under anesthesia, both the pylorus and limiting ridge were simultaneously ligated. One hour postligation, 0.3 ml of saline or ammonia at various concentrations was administered intragastrically by gastric intubation. Three hours after ligation, the animals were killed, the esophagus and stomach were removed, and the length of esophageal hemorrhagic erosions was measured. The incidence of RE was 100% (7/7) in the control group, 71% (5/7) in the low-ammonia group, 29% (2/7) in the middle-ammonia group, and 14% (1/7) in the high-ammonia group. The severity of lesions decreased in correspondence to increases in ammonia concentration. The development of RE was significantly inhibited by ammonia in a dose-dependent manner. This study indicates that ammonia protects against development of RE. A decreased amount of ammonia in the stomach might be related to the development of RE after H. pylori eradication therapy.

Helicobacter pylori eradication therapy for high-grade mucosa-associated lymphoid tissue lymphomas of the stomach with analysis of p53 and K-ras alteration and microsatellite instability.

Recent studies have shown that 70-80% of low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regress in response to eradication of Helicobacter pylori (H. pylori). However, there are no reports on whether gastric high-grade MALT lymphomas regress after H. pylori eradication. We performed H. pylori eradication therapy in 4 patients with stage I, high-grade MALT lymphoma after obtaining their informed consent. H. pylori infection was observed in all 4 patients. The patients were treated with proton-pump inhibitor-based eradication therapy for 1 or 2 weeks, and then underwent endoscopic examination and biopsy sampling. H. pylori eradication was achieved in all 4 patients. Six months after eradication treatment, 2 patients showed complete regression of the lymphoma and 2 patients showed no change. The 2 patients with non-responding lymphoma were then treated with an additional chemotherapy (CHOP regimen), whereupon the tumors completely regressed. These patients, followed-up at least 18 months after eradication treatment, showed no recurrence. We also examined genetic alteration of the p53 and K-ras genes and microsatellite instability in these high-grade MALT lymphomas. One patient with a tumor that showed no change after H. pylori eradication, had a loss of heterozygosity of the p53 gene. No other genetic alterations were detected among the patients. Our results indicate that the eradication of H. pylori may be effective not only for patients with low-grade MALT lymphoma but also for patients with high-grade MALT lymphoma. The treatment may be efficacious as a first-line therapy for patients with high-grade MALT lymphoma. However, our sample size was limited and further studies are needed to clarify the issue.

B-cell monoclonality in Helicobacter pylori-associated chronic atrophic gastritis.

B-cell monoclonality has been reported not only in gastric lymphoma, but also in 1.3-21% of Helicobacter pylori-associated chronic gastritis (Hp-CG) cases. The aim of this study was to determine the significance of B-cell monoclonality in Hp-CG. We examined 134 gastric biopsy specimens from 99 patients with Hp-CG. The density of Hp, polymorphonuclear neutrophil activity, chronic inflammation, glandular atrophy, and intestinal metaplasia (IM) were scored according to the updated Sydney System. B-cell monoclonality was analyzed for immunoglobulin heavy chain gene rearrangement using polymerase chain reaction amplification. B-cell monoclonality was detected in 6% of informative samples. B-cell monoclonality was found in 18% of the samples from Hp-CG patients with marked glandular atrophy but in none of the samples from Hp-CG patients with none to moderate glandular atrophy. Monoclonality was also detected in 20% of the samples from Hp-CG patients with marked IM, in 11% of the samples from Hp-CG patients with moderate IM, and in none of the samples from Hp-CG patients without IM. Therefore, B-cell monoclonality was significantly more frequent in Hp-CG patients with marked glandular atrophy than in Hp-CG patients with none to moderate atrophy. It was also more significantly frequent in Hp-CG patients with moderate or marked IM than in Hp-CG patients without IM (P < 0.05). Of 35 Hp-CG patients, 26 (74%) had identical B-cell populations in the antrum and the corpus, and all were polyclonal. The remaining nine (26%) Hp-CG patients had B-cell populations that differed in the antrum and the corpus. Four of the nine (44%) showed monoclonal B-cell populations in at least one gastric biopsy specimen. There were no patients with monoclonal B-cell populations in both the antrum and the corpus. These data suggest that glandular atrophy and IM in gastric biopsy specimens may be markers for gastric mucosa-associated lymphoid tissue (MALT) lymphoma-genesis and that multiple gastric biopsy specimens from both the antrum and the corpus may be needed to assess the risk of gastric MALT lymphoma.

Optimal time for predicting myocardial viability after successful primary angioplasty in acute myocardial infarction: a study using myocardial contrast echocardiography.

This study sought to elucidate serial changes in microvascular integrity during papaverine-induced hyperemia in the risk area for myocardial infarction. In addition, we attempted to determine the optimal time for predicting myocardial viability. Seventy-two patients who underwent serial myocardial contrast echocardiography (MCE) before and shortly after (day 1), 1 day (day 2), and 3 weeks (day 21) after recanalization were studied. In 18 of 72 patients, MCE was performed at baseline and during hyperemia using selective intracoronary infusion of papaverine. Both the peak grayscale ratio (PGSR) within the risk area, and the no- and low-reflow ratio (LR ratio) were analyzed in each stage. Left ventricular regional wall motion (RWM) was determined 6 months after recanalization. The correlation coefficient between PGSR with papaverine on day 1 and that on day 2 was 0.54 (p = 0.02); it was 0.50 (p = 0.04) between day 1 and day 21, and 0.82 (p = 0.001) between day 2 and day 21. On day 1, the correlation coefficient between the LR ratio with papaverine and RWM was 0.60 (p = 0.02), which changed to 0.72 (p = 0.003) on day 2 and 0.54 (p = 0.04) on day 21, respectively. The best time to predict viable myocardium was established on day 2 by receiver operating characteristics curves. ST-segment re-elevation, elapsed time from onset to recanalization, and antecedent angina pectoris were independent factors for PGSR on day 2 using stepwise and multiple linear regression analysis. This study suggests that the optimal time to estimate microvascular integrity for predicting myocardial viability might be 1 day after recanalization, which is neither shortly after recanalization nor during the convalescent stage.

Clinical significance of human erythrocyte glucose transporter 1 expression at the deepest invasive site of advanced colorectal carcinoma.

OBJECTIVE: Malignant cells exhibit increased glucose uptake and utilization in vitro and in vivo. This process is thought to be mediated by the glucose transporter (Glut) family. The aim of this study was to elucidate the clinical significance of Glut1 expression at the site of deepest invasion as a predictor of the invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). METHODS: One hundred and fifty-two patients who had undergone surgical resection for advanced CRC were entered in this study. Histologic subclassifications at the deepest invasive site included well-differentiated (W), moderately to well-differentiated (Mw), moderately to poorly differentiated (Mp), poorly differentiated (Por) and mucinous (Muc) adenocarcinomas. Glut1 expression was examined immunohistochemically with a labeled streptavidin-biotin kit using anti-Glut1 polyclonal antibody MYM. As a marker of cell proliferation, Ki-67 expression was also examined. All immunoreactivity was analyzed at the deepest invasive site, central portion and superficial part. The immunohistochemical expression of Glut1 was defined as positive if distinct staining of the membrane or cytoplasm was observed in at least 30% of tumor cells. RESULTS: Glut1 expression was detected in 56 of 152 lesions (36.8%) at the deepest invasive site. The incidence of Glut1 expression at the deepest invasive site correlated significantly with histologic grade (W/Mw grade, 28% vs. Mp/Por/Muc grade, 48%), depth of invasion (invasion of muscularis propria/invasion of subserosa or subadventitia, 29% vs. invasion of serosa or adventitia/invasion of adjacent structures, 52%), lymphatic invasion (absence of lymphatic invasion, 19% vs. presence of lymphatic invasion, 40%), lymph node metastasis (absence of lymph node metastasis, 25% vs. presence of lymph node metastasis, 41%) and Duke's stage (Duke's

c-myc gene mutation in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma.

The c-myc gene is involved in important cellular processes, including cell proliferation, differentiation, and apoptosis. We analyzed mutation of the c-myc gene in 51 patients with gastric lymphoma [27 patients with low-grade mucosa-associated lymphoid tissue (MALT) lymphoma, 11 with high-grade MALT lymphoma, and 13 with diffuse large B-cell lymphoma (DLL)], by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. We also evaluated the relationship between mutation of the c-myc gene and regression of low-grade MALT lymphoma after Helicobacter pylori (H. pylori) eradication. Mutation in exon 2 of the c-myc gene was present in 2 of 20 (10%) patients with low-grade MALT lymphoma, in 1 of 7 (14%) patients with high-grade MALT lymphoma, and none of 10 patients with DLL. The 3 patients who had mutations of the gene, showed different patterns of mobility shift, suggesting different mutations. In addition, 15 patients with low-grade MALT lymphoma received anti-H. pylori therapy. All the patients achieved eradication. Nine of the 15 (60%) patients with low-grade MALT lymphoma showed complete regression (CR), 3 (20%) showed partial regression (PR), and 3 (20%) showed no change (NC). One of the 9 (11%) CR patients had a mutation of the c-myc gene. None of the 3 PR and 3 NC patients had mutation of the gene. There was no significant difference between the frequencies among the c-myc gene mutation in CR, in PR and in NC patients. These data suggest that mutation of the c-myc gene may not be commonly associated with development of gastric MALT lymphoma and DLL, and may not be associated with regression of low-grade MALT lymphoma after H. pylori eradication.

Microsatellite instability at D18S61 is associated with no regression of gastric mucosa-associated lymphoid tissue lymphoma after Helicobacter pylori eradication.

Recent studies have shown 70-80% of gastric low-grade mucosa-associated lymphoid tissue (MALT) lymphomas regressing in response to eradication of Helicobacter pylori (H. pylori). Genetic mechanism of regression of gastric MALT lymphoma after H. pylori eradication remains unclear. To clarify the issue, we evaluated microsatellite instability (MSI) at 12 microsatellite loci in 15 patients with gastric low-grade MALT lymphoma, who received eradication therapy of H. pylori. H. pylori infection was observed in all the patients. After eradication therapy of H. pylori, patients were observed for a median of 21 months (range, 6-49 months). Eradication was achieved in all the patients. Nine of the 15 (60%) patients showed complete regression (CR), 3 (20%) partial regression (PR), and 3 (20%) no change (NC). MSI was detected in 3 of the 15 (20%) patients with low-grade MALT lymphoma. Compared with response to eradication therapy of H. pylori, MSI was detected in 1 of the 12 (8%) CR and PR patients, and in 2 of the 3 (67%) NC patients. Especially, MSI at D18S61 was detected in 2 of the 3 (67%) NC patients but in none of the 12 CR and PR patients. There was a significant difference between frequency of MSI at D18S61 in NC patients and that in CR and PR patients (p<0.05). These data suggest that MSI at D18S61 may be associated with lack of regression of gastric MALT lymphoma after H. pylori eradication.

Quinapril with high affinity to tissue angiotensin-converting enzyme reduces restenosis after percutaneous transcatheter coronary intervention.

Experimental studies have demonstrated that vascular injury resulted in an induction of vascular angiotensin-converting enzyme (ACE), and have suggested that inhibition of vascular ACE might be important in the prevention of restenosis. The present study aimed to determine the effect of quinapril, an ACE inhibitor with high affinity to tissue ACE, on restenosis following coronary intervention. The design of this study was a prospective, randomized, open, and non-placebo controlled trial. Patients with ischemic heart disease were enrolled after successful percutaneous transluminal coronary angioplasty or stent implantation at 7 participating institutions. Two hundred and fifty-three patients with 294 lesions were randomly assigned to the quinapril (10-20 mg per day) group or control group. Administration of quinapril was continued for 3-6 months of the follow-up. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Core laboratory measurements were performed independently and blinded. Follow-up angiography was performed in 108 patients with 124 lesions in the quinapril group and in 107 patients with 130 lesions in the control group. The baseline characteristics and findings of angioplasty showed no significant differences between the two groups. However, in the quinapril group, restenosis per patient and per lesion was significantly lower (34.3% vs. 47.7%, p < 0.05 and 30.6% vs. 43.8%, p < 0.05). Multivariable analysis revealed that administration of quinapril independently contributed to reducing the restenosis per patient and per lesion (odds ratio, 0.73; 95% confidence interval, 0.54-0.99 and odds ratio, 0.75; 95% confidence interval, 0.57-0.99). In conclusion, quinapril significantly reduces restenosis following coronary intervention.

Evaluation of flash echo imaging of the canine gastrointestinal tract.

Although it is important to assess gastrointestinal blood flow, no generally useful, noninvasive assessment method has been established. Harmonic flash echo imaging, which is an intermittent second harmonic imaging technique, has recently become available to evaluate blood flow. We investigated the usefulness of harmonic flash echo imaging in the assessment of the gastrointestinal tract, and we used this technique to study the effect of nicotine on small bowel blood flow. Harmonic flash echo imaging was performed at the beginning of intravenous injection of a contrast agent. It was also performed on the small bowel immediately before and 10 min after nicotine administration to evaluate blood flow. Gastric and small bowel walls were clearly enhanced on the primary images. Small bowel enhancement, which is regarded as transmural blood flow, significantly decreased after nicotine administration. Harmonic flash echo imaging appears to be useful in the assessment of the transmural blood flow in the gastrointestinal wall.

Real-time ultrasonographic assessment of antroduodenal motility after ingestion of solid and liquid meals by patients with functional dyspepsia.

BACKGROUND AND AIMS: Although antroduodenal motility has usually been studied by using manometric or scintigraphic methods, ultrasonography is an established, non-invasive method to evaluate duodenogastric motility. We used ultrasonography to evaluate gastric motility in patients with functional dyspepsia. METHODS: Sixty-four patients with functional dyspepsia and 36 asymptomatic healthy subjects were given liquid and solid test meals. We investigated the gastric emptying rate, motility index, and duodenogastric reflux for the liquid meal and gastric emptying time, half-emptying time, and motility index for the solid meal. RESULTS: After the liquid meal, the gastric emptying rate and motility index were significantly lower and the duodenogastric reflux was significantly higher in functional dyspepsia patients than in healthy subjects. After the solid meal, gastric emptying time, half-emptying time and the motility index were significantly lower in the patients than in the healthy subjects. Delayed gastric emptying of both meals occurred in only 20.3% of patients. Delayed emptying of the liquid or solid meal occurred in 62.5% of patients. In both groups, gastric emptying time of the solid meal was positively correlated with the motility index at 15 min post-ingestion. CONCLUSION: In functional dyspepsia patients, delayed gastric emptying of a solid meal was related to antral hypomotility during the early postprandial phase. Ultrasonographic assessment of gastric motility in both liquid and solid meals may provide a better understanding of the pathogenesis of functional dyspepsia.