Biomedical subjects

T Ohkusa

Publications and source records attributed to T Ohkusa.

At least 19 recordsLinked to original sources

PubMed2005

Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis.

BACKGROUND: The polymorphic enzyme cytochrome P450 2C19 affects omeprazole metabolism. This influence on metabolism might affect serum gastrin levels, and safety, during long-term treatment of reflux oesophagitis. AIM: To examine the relationship between cytochrome P450 2C19 genotype and the safety profile of long-term omeprazole treatment. METHODS: A total of 119 Japanese patients with recurrent reflux oesophagitis underwent cytochrome P450 2C19 genotyping prior to receiving daily omeprazole 10 mg or 20 mg for 6-12 months, during which adverse event frequency, serum gastrin levels and endoscopic findings were monitored. RESULTS: The incidences of adverse events, serious adverse events and adverse events leading to withdrawal did not differ between homozygous extensive metabolizer (n = 46), heterozygous extensive metabolizer (n = 53) or poor metabolizer (n = 20) groups. In all genotype groups, serum gastrin increased during the first 3 months of dosing but stabilized thereafter. No significant differences were seen either in the rate of reflux oesophagitis healing or symptom improvement among genotype groups. CONCLUSIONS: Long-term treatment with omeprazole was well-tolerated in Japanese patients, irrespective of their cytochrome P450 2C19 metabolic genotype, indicating that dose adjustment depending on metabolic genotype is not required during treatment with omeprazole.

Adult↗

PubMed2005

Mucosa-associated bacteria in ulcerative colitis before and after antibiotic combination therapy.

BACKGROUND: We proposed that Fusobacterium varium is one of the causative agents in ulcerative colitis. AIM: To examine the efficacy of antibiotic combination therapy against F. varium and to investigate the mucosa-associated bacteria before and after the therapy using a new molecular approach. METHODS: Twenty patients with ulcerative colitis were randomly assigned into the antibiotic treatment group (amoxicillin, tetracycline and metronidazole for 2 weeks) and no-antibiotics group. Clinical assessment, colonoscopic and histological evaluations were performed at 0 and 3-5 months after the treatment. DNA from mucosal bacteria was isolated from biopsy specimens. We investigated the mucosa-associated bacterial components by terminal restriction fragment length polymorphism with the restriction enzyme HhaI and MspI, and quantified the change in the number of bacteria by real-time polymerase chain reaction. Immunohistochemical detection of F. varium in biopsy specimens was also performed. RESULTS: After the treatment, the clinical assessment, colonoscopic and histological scores improved in the antibiotic group compared with the control group. Three peaks of terminal restriction fragment length polymorphism decreased after treatment only in the antibiotic group. Eubacterium rectale, Dorea formicigenerans, Clostridium clostridioforme and F. varium were included in these peaks. Based on the real-time polymerase chain reaction study, only F. varium was significantly reduced after treatment. In the immunostaining, post-treatment scores in treatment group were significantly lower than that in control group. CONCLUSIONS: Antibiotics combination therapy was effective for ulcerative colitis. The number of mucosa-associated F. varium significantly decreased after the treatment.

Amoxicillin↗

PubMed2004

Diagnostic performance of light-induced fluorescence endoscopy for gastric neoplasms.

BACKGROUND AND STUDY AIM: Malignant tumors generate autofluorescent patterns that differ from those of normal tissue. However, whether autofluorescent diagnosis could be genuinely useful in screening for gastric neoplasms has not been well investigated in clinical practice. Accordingly, we retrospectively studied our experience with this diagnostic technique for various gastric lesions and assessed its diagnostic utility. PATIENTS AND METHODS: Autofluorescence diagnosis of 109 gastric lesions in 79 patients was done, without knowledge of the diagnosis by conventional white light endoscopy, retrospectively and independently by three endoscopists with 6 years', two years' and no experience of the technique. After examination of the interobserver bias in the assessment of autofluorescent pseudocolor in light-induced fluorescence endoscopy (LIFE), the relationship between pseudocolor and characteristics of gastric lesions (including histology, macroscopic type, and depth of invasion) were investigated. RESULTS: The kappa statistic for agreement in pseudocolor diagnosis between the three endoscopists was 0.71. The assessment of pseudocolor by all of the observers was in agreement in 67 of the total of 109 lesions (61.5 %). Experience with the LIFE technique did not improve the accuracy of pseudocolor determination. All of the cancers, 87.5 % of the adenomas, and 50.9 % of the benign lesions were recognized as having an abnormal autofluorescent image. None of the gastric cancers and 49.1 % of the benign lesions were evaluated as having a normal autofluorescence image. The histopathological and macroscopic types of tumors and their depths of invasion were not reflected in the autofluorescence diagnosis. CONCLUSIONS: LIFE provided a sensitivity of 96.4 % and specificity of 49.1 %, suggesting that this technique has limited clinical utility, regardless of the merits of acceptable interobserver bias and lack of necessity for experience with this technique.

Adenocarcinoma↗

PubMed2004

Improvement in serum pepsinogens and gastrin in long-term monitoring after eradication of Helicobacter pylori: comparison with H. pylori-negative patients.

BACKGROUND: A decrease in pepsinogen and gastrin levels 1-3 months after Helicobacter pylori eradication is well known. However, few data are available on the long-term progression of these decreases beyond 1 year after eradication, and there has been no investigation into whether pepsinogen and gastrin levels return to normal levels as defined by data from H. pylori-negative patients with dyspepsia. AIM: We studied the effect of H. pylori eradication on pepsinogen and gastrin levels for more than 1 year, and compared levels to those in H. pylori-negative patients with dyspepsia. We also investigated the effect of H. pylori eradication on the course of atrophic corpus gastritis as reflected by histology, and on PGI levels and PG I/II ratio. METHODS: We enrolled 172 H. pylori-positive patients with dyspepsia who had undergone successful eradication therapy of more than 1 year's duration and 101 non-treated H. pylori-negative patients with dyspepsia. H. pylori status was assessed at entry and at each endoscopy after eradication by culture, histological results, the rapid urease test and the urea breath test. In both groups, patients were evaluated for fasting serum pepsinogen I and II and gastrin using a radioimmunoassay technique, and underwent detailed histological assessment according to the updated Sydney System. RESULTS: In the H. pylori-negative patients, mean serum pepsinogen I and II, I/II ratio and gastrin levels were 52.6 +/- 20.8 ng/mL, 9.2 +/- 4.2 ng/mL, 6.0 +/- 1.7 and 53.5 +/- 29.2 pg/mL, respectively. In H. pylori-positive patients with long-term eradication, pepsinogen I and II, I/II ratio and gastrin levels were 81.3 +/- 46.6 ng/mL, 25.9 +/- 17.1 ng/mL, 3.4 +/- 1.3 and 131.9 +/- 130.8 pg/mL, respectively, before treatment. At 1-3 months after eradication, serum pepsinogen I and II levels in the H. pylori-positive patients decreased to levels similar to those in the negative patients, whereas pepsinogen I/II ratio and gastrin levels remained lower and higher, respectively, than in the negative patients. Serum pepsinogen I/II ratio and gastrin levels then became similar between the groups at 12-15 months after eradication. In histological findings, inflammation and neutrophil activity decreased by 1-3 months, and atrophy in the corpus and metaplasia in the antrum decreased by 12-15 months. CONCLUSION: The results suggest that atrophic corpus gastritis and superficial gastritis are reversible, as indicated by both histological and serological findings in a long-term follow-up study.

Dyspepsia↗

PubMed2004

Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. AIM: To investigate oesophageal hypersensitivity in Japanese NERD patients. PATIENTS AND METHODS: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. RESULTS: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 +/- 3.4, 4.4 +/- 3.4, 27.8 +/- 26.7, respectively) were higher than in erosive GERD (3.2 +/- 3.3, 3.0 +/- 3.2, 18.2 +/- 24.8) and Barrett patients (2.5 +/- 4.0, 1.8 +/- 3.3, 15.0 +/- 28.8), and significantly higher than in the control group (1.7 +/- 2.7, 1.1 +/- 2.0, 5.4 +/- 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). CONCLUSION: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Adult↗

PubMed2004

Down-regulation of sarcolipin mRNA expression in chronic atrial fibrillation.

BACKGROUND: Abnormal intracellular Ca2+ homeostasis is an important modulator of chronic atrial fibrillation. Sarcolipin, a homologue of phospholamban, is specifically expressed in the atria, and may play an important role in modulating intracellular Ca2+ homeostasis in the atria. The aim of this study was to investigate the expression of sarcolipin mRNA in the atrial myocardium of patients with chronic atrial fibrillation. METHODS: We analyzed the expression of sarcolipin, phospholamban, cardiac calsequestrin and sodium calcium exchanger mRNAs in the right atrial myocardium from nine patients with mitral valvular disease with atrial fibrillation (MVD/AF), nine patients with MVD who had normal sinus rhythm (MVD/NSR), and 10 control patients with normal sinus rhythm who received open heart surgery (controls). The expression of mRNA was measured using the ABI PRISM 7700 Sequence Detection System (Applied Biosystems, Foster City, CA). RESULTS: Relative expression levels of sarcolipin mRNA were significantly lower in MVD/AF (0.60 +/- 0.11) than in either MVD/NSR (1.28 +/- 0.17, P < 0.01) or controls (1.10 +/- 0.10, P < 0.05). The expression levels of sarcolipin mRNA were significantly lower in the group with high values for right atrial pressure. The expression levels of phospholamban, cardiac calsequestrin and sodium calcium exchanger mRNAs were comparable among all three groups. CONCLUSIONS: Chronic electrical and mechanical overload decreased the expression of sarcolipin mRNA in the right atrial myocardium in patients with chronic atrial fibrillation. Down-regulation of sarcolipin mRNA may be part of atrial fibrillation-induced atrial remodelling.

Adult↗

PubMed2003

Is antimicrobial susceptibility testing necessary before second-line treatment for Helicobacter pylori infection?

BACKGROUND: An antimicrobial susceptibility test for Helicobacter pylori before second-line treatment is often performed, although whether the test is truly necessary remains unknown. PATIENTS AND METHODS: Eighty-two patients with H. pylori infection for whom first-line treatment with a 1-week proton pump inhibitor/amoxicillin-clarithromycin (AC) regimen had failed were randomly assigned to two groups: those having or not having the susceptibility test before re-treatment. The cure rates for these two groups were compared. RESULTS: Five of the 82 patients were excluded from the analysis. For 38 patients in the susceptibility-test group, we used what we considered the best regimen based on susceptibility testing: 10 patients [no resistance to clarithromycin (CAM)] received the lansoprazole-amoxicillin-clarithromycin regimen, 22 patients [19 CAM resistant, metronidazole (MNZ) susceptible; three failure of culture] were given the lansoprazole-amoxicillin-metronidazole (LAM) regimen, and six patients (both MNZ and CAM resistant) received dual therapy with omeprazole (OPZ) and amoxicillin (AMOX) in which the OPZ dose was determined by the CYP2C19 gene polymorphism. For 39 patients in the group with no susceptibility testing, LAM regimens were prescribed. The intention-to-treat (ITT)-based cure rates in the groups with and without susceptibility testing were 81.6% (95% confidence interval; 66-92%) and 92.4% (79-98%), respectively, and there was no significant difference between these two groups. CONCLUSION: Susceptibility testing is not necessarily required before second-line therapy if the first-line treatment has been performed using proton pump inhibitor/AC regimens.

Adult↗

PubMed2003

Induction of experimental ulcerative colitis by Fusobacterium varium isolated from colonic mucosa of patients with ulcerative colitis.

BACKGROUND: Bacteria are implicated in certain forms of model chronic colitis but the identity and role of bacteria in human ulcerative colitis (UC) are uncertain. AIMS: To isolate pathogenic bacteria from inflamed mucosa of patients with UC, to examine whether the bacteria have a toxin to Vero cells, and to determine whether the toxin induces UC-like lesions in animals. METHODS: Bacteria were isolated from UC patients and supernatants from cultures were filtered and tested for cytotoxicity to Vero cells. Bacterial cells producing the cytotoxic supernatants were examined by polymerase chain reaction for verotoxin genes. Culture supernatants of cytotoxic strains were examined by high performance liquid chromatography for organic acid concentrations. Mice were given enemas containing organic acid at the mean concentration in the supernatants of cytotoxic strains to ascertain whether colonic lesions appear in UC. RESULTS: Only supernatants from cultures of Fusobacterium varium killed Vero cells. Bacterial cells lacked verotoxin genes. Bacterial culture supernatants contained high concentrations of n-butyric acid and the mean concentration (32 mmol/l) was cytotoxic to Vero cells. Twenty four hours after mice were given enemas containing either butyric acid or F varium culture supernatants, colonic ulcers with crypt abscesses, inflammatory cell infiltration, and apoptotic changes were observed. CONCLUSIONS: Butyric acid in culture supernatants from cultures of F varium caused UC-like lesions in mice. This study indicates that F varium may be one of the elusive pathogenic factors in UC.

Adult↗

PubMed2003

Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils.

BACKGROUND: There is no direct evidence for an animal model of Helicobacter pylori induced duodenal ulcer. AIM: In this study we evaluated the roles of bacterial strain and age of experimental animals in induction of duodenitis and duodenal ulcer in Mongolian gerbils after H pylori infection. METHODS: Specific pathogen free Mongolian gerbils were inoculated orally with three bacterial strains (H pylori ATCC 43504, TN2GF4, and K-6, a clinical isolate from a patient with gastric cancer in our clinic). These strains have both the cagA gene and VacA. Five week old gerbils were used to emulate prematurity infection and 14 week old animals were used as mature test subjects. Animals were observed for 12 weeks after inoculation. Interleukin 8 (IL-8) production in gastric epithelial cells (MKN74) after coculture with the H pylori strains was measured by ELISA. RESULTS: Gastritis and gastric ulcers were found in all gerbils infected with the three strains. However, duodenitis and gastric metaplasia were seen more frequently in gerbils infected with TN2GF4 and K-6 strains than in the ATCC 43504 infected or control groups (p<0.05). Superficial duodenal ulcers with severe duodenitis and gastric metaplasia were found in two gerbils inoculated at 14 weeks with the TN2GF4 strain but none at five weeks. The TN2GF4 strain stimulated significantly higher levels of IL-8 than ATCC 43504 and K6 strains (p=0.0039). CONCLUSIONS: When injected into adult Mongolian gerbils, a specific strain (TN2GF4) of H pylori can induce duodenitis with gastric metaplasia and superficial duodenal ulcers. Induction of duodenal ulcer in an animal model fulfills the requirements of Koch's postulates for establishing a role for H pylori as a causative agent.

Age Factors↗

PubMed2002

Alteration of histological gastritis after cure of Helicobacter pylori infection.

BACKGROUND: It is still disputed whether gastric atrophy or intestinal metaplasia improves after the cure of Helicobacter pylori infection. AIM: To clarify the histological changes after the cure of H. pylori infection through a literature survey. METHODS: Fifty-one selected reports from 1066 relevant articles were reviewed. The extracted data were pooled according to histological parameters of gastritis based on the (updated) Sydney system. RESULTS: Activity improved more rapidly than inflammation. Eleven of 25 reports described significant improvement of atrophy. Atrophy was not improved in one of four studies with a large sample size (> 100 samples) and in two of five studies with a long follow-up period (> 12 months), suggesting that disagreement between the studies was not totally due to sample size or follow-up period. Methodological flaws, such as patient selection, and statistical analysis based on the assumption that atrophy improves continuously and generally in all patients might be responsible for the inconsistent results. Four of 28 studies described significant improvement of intestinal metaplasia [corrected]. CONCLUSIONS: Activity and inflammation were improved after the cure of H. pylori infection. Atrophy did not improve generally among all patients, but improved in certain patients. Improvement of intestinal metaplasia was difficult to analyse due to methodological problems including statistical power.

Gastric Mucosa↗

PubMed2002

Gastric mucosal density of Helicobacter pylori estimated by real-time PCR compared with results of urea breath test and histological grading.

The accuracy of the urea breath test (UBT) and histological grading for estimation of the density of Helicobacter pylori in gastric mucosa is not known. Real-time (TaqMan) PCR was used to estimate the total number of H. pylori genomes in biopsy samples. These values were compared with those obtained by the UBT and the histological grade obtained by the Sydney system. The UBT and endoscopy with antral and corporal biopsies were performed in 88 consecutive untreated patients with dyspepsia. Bacterial culture and the rapid urease test were done with fresh biopsy materials. TaqMan PCR and histological examination were done on serial paraffin sections of the biopsy samples. Of the five methods tested, TaqMan PCR had the highest sensitivity and specificity (both 100%) in the diagnosis of H. pylori infection. The mean density of H. pylori genomes for pairs of biopsy samples from individual patients was compared with the individual values obtained by the UBT; correlation between the results was significant. The density of H. pylori genomes was higher in histological grades 1, 2 and 3 than in grade 0, without significant differences between adjacent grades from 1 to 3. These results suggest that the severity of H. pylori infection of the stomach can be estimated by the UBT and that histopathologists might state whether the organism is present or absent, rather than making a quantitative statement as recommended in the Sydney system.

Biopsy↗

PubMed2001

Calcium handling and sarcoplasmic-reticular protein functions during heart-failure transition in ventricular myocardium from rats with hypertension.

The objective of this study was to determine the primary event that occurs in Ca2+-regulatory sarcoplasmic-reticular (SR) proteins during subacute transition from concentric/mechanically-compensated left ventricular (LV) hypertrophy to eccentric/decompensated hypertrophy. Using Dahl salt-sensitive rats with hypertension, changes of myocardial contraction, intracellular Ca2+ transients, SR Ca2+ uptake, protein levels of SR Ca2+ ATPase (SERCA2), phospholamban, and calsequestrin (CSQ), and mRNA levels of SERCA2 and CSQ were serially determined and compared between the established stage of LV hypertrophy (LVH) and the subsequent stage of overt LV dysfunction (CHF). In LVH, isolated LV papillary muscle preparations showed an equal peak-tension level and a mild prolongation of the isometric tension decay compared to those of age-matched controls. The Ca2+ transients as measured by aequorin were unchanged. The Ca2+ uptake of isolated SR vesicles and the protein/mRNA levels of SR proteins were also equivalent to those of the controls. In contrast, in CHF, the failing myocardium showed a further prolongation of the contraction time course and a 39% reduction of the peak-tension development. The Ca2+ transients showed changes consisting of a decrease in the peak level and a prolongation of the time course. In addition, the SR Ca2+ uptake was decreased by 41%. Despite these functional changes, the protein and mRNA levels of the SR components remained equivalent to those of the age-matched controls. Thus, in this hypertensive animal, 1) at the LVH stage, myocardial contractility and intracellular capability to regulate Ca2+ remained normal; 2) at the CHF stage, impaired SR Ca2+ handling and the subsequent reduction of myocardial contraction were in progress; and 3) impairments of SR function occurred at the post-translational protein level rather than at the transcriptional/translational levels. Our findings support the role of SR proteins as the primary determinant of the contractile dysfunction that occurs during the heart-failure transition; however, post-translational modulators of these SR elements may also be critical.

Aequorin↗

PubMed2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗

PubMed2001

Up-regulation of inositol 1,4,5 trisphosphate receptor expression in atrial tissue in patients with chronic atrial fibrillation.

OBJECTIVES: We examined whether patients with atrial fibrillation (AF) have alterations in atrial inositol 1,4,5 trisphosphate receptors (IP3 receptors). BACKGROUND: Abnormal intracellular Ca2+ homeostasis occurs in chronic AF. The intracellular Ca2+ concentration is regulated by ryanodine and IP3 receptors. We recently reported alterations in ryanodine receptors in atrial tissue from patients in chronic AF. METHODS: We analyzed IP3 receptor expression in the right atrial myocardium from 13 patients with mitral valvular disease (MVD) with AF (MVD/AF), five patients with MVD who had normal sinus rhythm (MVD/NSR) and eight control patients with NSR (tissue obtained during coronary artery bypass surgery). Hemodynamic and echocardiographic data were obtained preoperatively, and an immunohistochemical study was performed on atrial tissue. RESULTS: The relative expression level of IP3 receptor protein was significantly greater in MVD/AF (0.75 +/- 0.26) than it was in MVD/NSR (0.42 +/- 0.13, p < 0.01), and both were significantly above control (0.14 +/- 0.08). The relative expression level of IP3 receptor messenger RNA was significantly greater in the MVD/AF group (0.028 +/- 0.008) than it was in the control group (0.015 +/- 0.004, p < 0.01), but patients with MVD/AF did not differ from patients with MVD/NSR (0.020 +/- 0.006). The relative expression levels of IP3 receptor protein and messenger RNA were higher in patients with left atrial dimension > or = 40 mm, pulmonary capillary wedge pressure > or = 10 mm Hg and right atrial pressure > or = 5 mm Hg. Inositol 1,4,5 trisphosphate receptors were over-expressed in the cytosol and at the nuclear envelope of atrial myocytes in MVD. CONCLUSIONS: Since chronic mechanical overload of the atrial myocardium increased IP3 receptor expression, especially in patients with chronic AF, up-regulation of IP3 receptors may be important in modulating intracellular Ca2+ homeostasis and initiating or perpetuating AF.

Aged↗

PubMed2001

Improvement in atrophic gastritis and intestinal metaplasia in patients in whom Helicobacter pylori was eradicated.

BACKGROUND: Glandular atrophy and intestinal metaplasia are precancerous lesions; whether Helicobacter pylori eradication affects these lesions is controversial. OBJECTIVE: To determine whether H. pylori eradication is associated with improvement in glandular atrophy and intestinal metaplasia after at least 1 year. DESIGN: Single-blind, uncontrolled prospective trial. SETTING: Academic gastroenterology clinic in Japan. PATIENTS: 163 consecutive patients with dyspepsia and H. pylori infection. INTERVENTION: One-week course of a proton-pump inhibitor and antibiotic therapy. MEASUREMENTS: Endoscopic examination with antral and corporal biopsy was done before treatment and at 1 to 3 and 12 to 15 months after treatment. Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System. RESULTS: In the 115 patients in whom H. pylori was eradicated, inflammation and mean neutrophil activity had decreased by 1 to 3 months, and both glandular atrophy in the corpus and intestinal metaplasia in the antrum had decreased by 12 to 15 months. Glandular atrophy in the corpus improved in 34 (89%) of 38 patients with atrophy before treatment, and intestinal metaplasia in the antrum improved in 28 (61%) of 46 patients who had metaplasia at baseline. In the 48 patients in whom eradication was unsuccessful, no significant histologic changes were observed. CONCLUSION: In the year after successful H. pylori eradication, precancerous lesions improved in most patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Enhancement of Rho/Rho-kinase system in regulation of vascular smooth muscle contraction in tachycardia-induced heart failure.

OBJECTIVE: The Rho/Rho-kinase system regulates Ca(2+) sensitivity in vascular smooth muscle. A new drug, Y-27632, specifically inhibits Rho-kinase and hence decreases the phosphorylation of myosin light chain, thus reducing contraction. Here, we compare the effects of Y-27632 and nifedipine on the vasoconstrictor response of the femoral artery in heart failure. METHODS: Heart failure (HF) was produced by chronic rapid RV pacing (250 bpm, 28 days, six dogs). Indo1-AM was loaded into endothelium-denuded femoral artery segments for measuring intracellular [Ca(2+)]. Tension and changes in intracellular [Ca(2+)] [the change in the ratio (418 nm/468 nm) of Indo1 fluorescence (F(ratio))] were simultaneously measured in Krebs-Ringer solution. RESULTS: In HF: (i) norepinephrine (10 microM) produced greater tension (784+/-52 g/cm(2)) than in control (502+/-64 g/cm(2)) despite a similar increase in F(ratio), indicating increased Ca(2+) sensitivity in vascular smooth muscle; (ii) nifedipine attenuated this enhanced response by only a maximum of 27% at 1 micromol/l with a 56% reduction in F(ratio); (iii) Y-27632 attenuated it by a maximum of 80% at 100 micromol/l without a significant change in F(ratio); (iv) RhoA protein and mRNA expression levels in the femoral artery were up-regulated by +110% and +56%, respectively, while those of Rho-kinase were unchanged. CONCLUSIONS: The Ca(2+)-sensitizing mechanism involving the Rho/Rho-kinase system may be deeply involved in the enhanced arterial vasoconstriction seen in HF. Since Y-27632 attenuated this response in small arteries, it shows potential as a novel, potent vasodilator for the treatment of HF.

Amides↗

PubMed2001

Influence of climatic factors in the incidence of upper gastrointestinal bleeding.

BACKGROUND AND AIM: Previous reports have indicated seasonal fluctuations in the incidence of peptic ulcer activity, but the reasons for the seasonal pattern are not clear. We assessed the seasonal incidence of hematemesis caused by peptic ulcers or gastroesophageal varices, and the correlations between those and climatic factors. METHODS: We examined the number of cases of upper gastrointestinal (GI) bleeding caused by gastric ulcer (GU), duodenal ulcer (DU), or gastroesophageal varices (varix) diagnosed by urgent endoscopies between 1 January 1996 and 31 December 1999 in our hospital (Tokyo Metropolitan Bokutou Hospital). We evaluated the monthly and seasonal incidence of them and investigated correlations among the incidence and climatic factors. RESULTS: Four hundred and forty-one patients participated in this study, including 275 patients with GU (62.4%), 51 (11.6%) with DU, and 115 (26.0%) with varix. The number of cases of hematemesis caused by GU showed significant monthly and seasonal fluctuations (P = 0.0002, P = 0.0018): it decreased in summer and increased in autumn-winter. Moreover, there were inverse relations between the monthly number of cases of hematemesis caused by GU and the mean temperature (P = 0.0016) and vapor pressure (P = 0.0013), and a parallel relation to the mean atmospheric pressure (P = 0.0057). In contrast, the number of cases of hematemesis caused by DU and varices did not show any monthly or seasonal fluctuations. CONCLUSIONS: We found that the incidence of hematemesis because of GU had an inverse relationship to temperature and vapor pressure, and had a parallel relation to atmospheric pressure. Therefore, climatic factors may play an important role in hemorrhage from GU.

Climate↗

PubMed2001

High risk of Helicobacter pylori infection in young Japanese dentists.

BACKGROUND AND AIM: The route of person-to-person transmission of Helicobacter pylori may be either fecal-oral or oral-oral, because the bacterium is found in both dental plaque and feces. We assessed the prevalence of H. pylori seropositivity, which reflects present or past infection, in Japanese dentists exposed occupationally to dental plaque. METHODS: We examined the sera of 60 dentists (34 who were 20-29 years or older, and 26 who were over 30 years of age) and 60 age-matched controls by using quantitative ELISA for antibodies of the immunoglobulin G class to H. pylori. RESULTS: The proportion of dentists seropositive for H. pylori (42 of 60, 70%) was higher than in controls (23 of 60, 38%). The odds ratio for H. pylori seropositivity (3.8; 95% CI, 1.76-8.02) was high in the dentists. When dentists were classified in terms of the length of their practice, the odds ratio for seropositivity (10.4; 95% CI, 3.26-32.85) was high in the dentists practising for fewer than 4 years. The proportion of dentists in their 20s who were seropositive was greater than that in the group of age-matched controls. CONCLUSION: Japanese young dentists are at a high risk for H. pylori infection, with the oral-oral transmission route being possibly the most common.

Adult↗