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Biomedical subjects

K Kihira

Publications and source records attributed to K Kihira.

At least 19 recordsLinked to original sources
PubMed1999

Amnesic effects of the anticholinergic drugs, trihexyphenidyl and biperiden: differences in binding properties to the brain muscarinic receptor.

An amnesic effect of anticholinergic drugs was previously described from several behavioral studies. We examined this effect induced by trihexyphenidyl and biperiden, clinically used in the parkinsonism and schizophrenic patients, by using passive avoidance tasks. Both of these drugs (0.1-10 mg/kg, s.c.) showed dose-dependent amnesic effects in the acquisition and retrieval phases. However, the effect induced by trihexyphenidyl was transient, whereas that of biperiden was long-lasting. To clarify the reason for the different duration of the amnesic activity, binding to the muscarinic receptor was examined. In the Scatchard analysis, trihexyphenidyl competed with [(3)H]quinuclidinyl benzilate ([(3)H]QNB) on the muscarinic receptor (showed increased K(d) and unchanged B(max) value), while biperiden decreased [(3)H]QNB binding (B(max) value) significantly. Furthermore, in an exchange assay for receptor inactivation, trihexyphenidyl binding to muscarinic receptors was exchanged by [(3)H]QNB completely, but biperiden decreased the exchangeable binding of [(3)H]QNB in a dose dependent manner (0.1-100 nM). These results suggested that the binding of trihexyphenidyl and biperiden to muscarinic receptor might be completely reversible and partially irreversible, respectively, whereas the K(i) values of these two drugs were similar. In conclusion, this difference in binding property may explain the difference in the time-course of the amnesic effect induced by trihexyphenidyl and biperiden.

Amnesia↗
PubMed1999

CagA and cytotoxicity of Helicobacter pylori are not markers of peptic ulcer in Japanese patients.

BACKGROUND: The infection with cagA-positive Helicobacter pylori strains is reported to be associated with peptic ulcer disease in developed countries, but it is controversial in Asia. To investigate the relationship between the virulence factors of H. pylori and peptic ulcer disease in Japan, we compared these between ulcer and nonulcer patients. MATERIALS AND METHODS: Seventy-four strains of clinically isolated H. pylori obtained from 22 gastric ulcer (GU), 23 duodenal ulcer (DU), and 29 chronic gastritis (CG) patients were studied. The presence of vacA and cagA gene was examined by polymerase chain reaction method using two different primer sets. We evaluated the proliferation-inhibiting and lethal cytotoxicity of culture supernatants using the alamarBlue assay. RESULTS: The vacA gene was identified in all strains by the original primers. S1 strains were found in 90.9% (20/22) from GU, 95.7% (22/23) from DU, and 96.6% (28/29) from CG patients. The prevalence of cagA gene determined by the first, and second primers was 90.9% (20/22), 90.9% (20/22) in strains from GU, 87.0% (20/23), 91.3% (21/23) from DU, and 86.2% (25/29), 89.7% (26/29) from CG patients, respectively. The supernatant showed cytolethal effect in 95.5% (21/22) of strains from GU, in 100% (23/23) from DU, and in 93.1% (27/29) from CG patients. There was no significant difference in the prevalence of the virulence factors between H. pylori strains isolated from patients with peptic ulcers and those with chronic gastritis. CONCLUSIONS: These results indicate that cagA gene status and the proliferation-inhibiting and lethal cytotoxicity of supernatant are not reliable markers of ulcerogenicity of H. pylori in Japanese patients.

Adolescent↗
PubMed1999

[Triple therapy regimens involving H2 blockaders for therapy of Helicobacter pylori infections].

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection. To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection, 99 patients with H. pylori infection were treated with either lansoprazole (LPZ) or ranitidine (RNT) used together with clarithromycin (CAM) and metrinidazole (MTZ). The drug combination and administration periods in the PPI group were LPZ 30 mg, CAM 400 mg, MTZ 500 mg (LCM group). The ranitidine group received RNT 300 mg, CAM 400 mg, MTZ 500 mg (RCM group). The cure rate of H. pylori infection was 88% in the LCM group; 95% CI 79-97 and 92% in the RCM group; 95% CI 84-99.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

[Changes in the severity of atrophic gastritis after Helicobacter pylori eradication].

There is a diversity of opinions as to whether Helicobacter pylori eradication leads to the improvement or regression of atrophic gastritis and intestinal metaplasia (IM), which are considered precursor lesions of intestinal type gastric cancer. We have made a 1.5-yr follow-up study after H. pylori eradication, but no significant improvement of atrophy or IM has so far been found. Some other factors than H. pylori may also play an important part in the development and progress of atrophic gastritis. The discrepancy between our data and others may be caused in part by the different methods of assessment of the grade of atrophy and sampling of biopsies.

Follow-Up Studies↗
PubMed1998

Biopsy sites suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis.

OBJECTIVES: We performed this study to determine which biopsy sites in the stomach are suitable for the diagnosis of Helicobacter pylori infection and the assessment of the extent of atrophic gastritis. METHODS: Endoscopy was performed in 76 H. pylori-positive patients with histologically confirmed chronic gastritis. Biopsies were taken from the following six sites: the lesser curvatures of the mid-antrum (site 1), the angulus (site 2), the middle body (site 3), and the greater curvatures of the mid-antrum (site 4), the angulus (site 5), and the middle body (site 6) of the stomach. The extent of atrophic gastritis was assessed endoscopically as well as histologically, and patients were classified into five groups according to its extent. H. pylori status was assessed histologically. The histological severity of inflammation, activity, atrophy, and intestinal metaplasia was assessed according to the Updated Sydney System. The grades of these items were compared among the six biopsy sites in each group of patients. RESULTS: Site 6 was most reliable for the diagnosis of H. pylori infection, and site 4 was suitable for examining the status of H. pylori colonization in the antrum. Site 1, site 3, and site 6 were suitable for the assessment of the extent of atrophic gastritis. CONCLUSIONS: Our results indicate that for an accurate diagnosis and assessment, biopsies should be taken from the following four sites: the lesser curvatures of the mid-antrum (site 1) and middle body (site 3), and the greater curvatures of the mid-antrum (site 4) and middle body (site 6) of the stomach.

Adult↗
PubMed1998

A follow-up study of atrophic gastritis and intestinal metaplasia after eradication of Helicobacter pylori.

BACKGROUND: Opinions differ as to whether atrophic gastritis and intestinal metaplasia (IM) improve after Helicobacter pylori eradication. We investigated the change of the severity of atrophy and IM after H. pylori eradication. MATERIALS AND METHODS: Twenty H. pylori-positive patients with histologically confirmed atrophic gastritis received anti-H. pylori therapy and achieved eradication. They were followed for 12-33 months (median 17 months) after the therapy. Biopsies were taken from the lesser and greater curvatures of the mid-antrum and middle body, and the incisura angularis of the stomach. The state of H. pylori infection was assessed histologically (Giemsa stain). Histological severity of atrophy and IM was graded according to the Updated Sydney System and scored on a 0-3 scale. The scores of atrophy and IM were compared between before and after the therapy (at the end of follow-up). RESULTS: No significant difference was found in the scores of antral or body atrophy between before and after the therapy. Scores of antral IM increased after the therapy, whereas those of body IM did not change significantly. Development of IM in the whole stomach was found in three of seven patients who had no IM before the therapy. All of them were male smokers and drinkers. In contrast, complete regression of IM was not found. CONCLUSIONS: Our results cast doubt on the reversibility of atrophy and IM after H. pylori eradication. Development of IM could be found in some of patients with atrophy even after H. pylori eradication.

Adult↗
PubMed1997

Comparison of ranitidine and lansoprazole in short-term low-dose triple therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy and safety of two 1-week low-dose triple-therapy drug regimens involving antisecretory drugs for Helicobacter pylori infection. 99 patients with H. pylori infection were treated with either lansoprazole or ranitidine used together with clarithromycin and metronidazole. METHODS: The drug combination and administration periods in the proton pump inhibitor group were lansoprazole 30 mg o.m., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d., all given for 7 days (LCM group). The ranitidine group received ranitidine 150 mg b.d., clarithromycin 200 mg b.d. and metronidazole 250 mg b.d. also for 7 days (RCM group). The presence or absence of H. pylori was determined from gastric biopsy specimens taken from both the antrum and the body, by smear, culture and tissue section (Giemsa stain). Cure was defined as failure to find evidence of H. pylori infection 4 weeks after antimicrobial therapy had ended. RESULTS: The cure of H. pylori infection was 88% in the LCM group (44 of 50; 95% confidence interval (CI) = 79-97%) and 92% in the RCM group (45 of 49; 95% CI = 84-99%). The incidence of adverse events was 16% and 18% for the two groups, respectively. CONCLUSIONS: No significant differences in cure rate and safety profiles were noted between the two regimens, suggesting that moderate acid inhibition using an H2-blocker is sufficient to achieve optimal H. pylori eradication.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

The value of LYM-1 cells for examining vacuole formation and loss of cell viability induced by culture supernates of Helicobacter pylori.

Some strains of Helicobacter pylori are known to produce an extracellular cytotoxin that causes vacuolation in cultured mammalian cells. Screening for such strains makes use of HeLa cells which may not be sensitive enough to detect minimal changes. The aim of this study was to develop a more sensitive cell line. Vacuole formation was examined in HeLa cells, as well as four other cell lines established in this laboratory by ammonium chloride induction. Among five cell lines tested, LYM-1 cells were most sensitive for the detection of intracellular vacuolation with this agent. Loss of cell viability of LYM-1 and HeLa cells induced by H. pylori culture supernates was also examined: LYM-1 were more sensitive than HeLa cells. Cell death was not always accompanied by vacuole formation. This suggests that the mechanism whereby cell death occurs must be different from that for vacuole formation. LYM-1 cells may be useful when measuring vacuole formation and cell death of the cultured cells induced by culture supernates of clinical isolates of H. pylori.

Ammonium Chloride↗
PubMed1997

The efficacy and safety of one-week triple therapy with lansoprazole, clarithromycin, and metronidazole for the treatment of Helicobacter pylori infection in Japanese patients.

BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of 1-week, low-dose triple therapy with lansoprazole, clarithromycin, and metronidazole (LCM) for the cure of H. pylori infection and to establish the adequate dosage of a new triple therapy for Japanese patients. MATERIALS AND METHODS: One hundred four H. pylori-positive Japanese patients were assigned alternatively to one of two groups: one to receive either 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily for 1 week (LCM1; n = 52); the other to receive 30 mg lansoprazole once in the morning, 200 mg clarithromycin twice daily, and 500 mg metronidazole twice daily for 1 week (LCM2; n = 52). H. pylori infection was assessed by smear, culture, and histological assessment (Giemsa stain) performed before and 4 weeks after cessation of the therapy. RESULTS: The overall cure rates of H. pylori infection were 92.3% (48 of 52; 95% confidence interval (CI), 85% to 100%) in LCM1 and 92.3% (48 of 52; 95% CI, 85% to 100%) in LCM2. The cure rates in the patients without prior treatment were 95.7% (44 of 46; 95% CI, 89%-100%) in LCM1 and 95.7% (45 of 47; 95% CI, 89%-100%) in LCM2. Minor side effects were observed in 7.7% of LCM1 and 9.6% of LCM2, respectively. CONCLUSION: The LCM1 regimen consisting of 30 mg lansoprazole once daily, 200 mg clarithromycin twice daily, and 250 mg metronidazole twice daily (the regular doses in ordinary use in Japan) is a highly effective and safe regimen for Japanese patients. LCM1 as a new triple therapy is a promising regimen for the first-line treatment of H. pylori infection in Japanese patients.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Deficiencies of automatic endoscopic reprocessors: a method to achieve high-grade disinfection of endoscopes.

BACKGROUND: We show that disinfection using the automatic endoscopic reprocessor is not complete and propose a method for high-grade disinfection of endoscopes. METHODS: We used an automatic endoscopic reprocessor, Pyser System 83, and 2% glutaraldehyde. After each endoscopic procedure, the endoscopes were divided into three groups. Endoscopes in group A were washed only by the reprocessor. Group B endoscopes were washed by the reprocessor after the connectors were soaked in glutaraldehyde for 5 minutes. The channels, valves, connecting sections of group C endoscopes, and the connectors of the machine were sprayed with glutaraldehyde before machine-washing. Swabs were taken from all 13 parts of each endoscope and machine for microbiologic culture. RESULTS: Six endoscopes were positive, cumulatively, for bacterial contamination in group A. Among group B endoscopes, one remained contaminated. No endoscope was positive in group C. The difference between group A and C was statistically significant (p < .05). CONCLUSIONS: Machine washing by automatic endoscopic reprocessors may not achieve complete disinfection. Additional procedures are necessary. High-grade disinfection of the connectors is critical. Disinfection of the interface between the connectors is important.

Disinfection↗
PubMed1996

Distribution of inflammation and atrophy in the stomach of Helicobacter pylori-positive and -negative patients with chronic gastritis.

OBJECTIVES: To investigate the extent of inflammation and atrophy in the stomach of Helicobacter pylori-positive and -negative patients with chronic gastritis. METHODS: Endoscopy with biopsies from the lesser curvatures of the antrum, angulus, middle body, and the greater curvature of the middle body of the stomach was performed in 59 patients with histologically confirmed chronic gastritis. The extent of atrophic gastritis was assessed endoscopically as well histologically. H. pylori status was assessed by histology as well as enzyme-linked immunosorbent assay. The histological severity of chronic and acute inflammation, glandular atrophy, and intestinal metaplasia was assessed according to the Sydney system. RESULTS: In H. pylori-positive patients, H. pylori was evenly distributed throughout the stomach when the extent of atrophic gastritis was limited to the antrum and the lesser curvature of the body, but disappeared from the antrum of patients with more extensive atrophic gastritis. The severity of acute and chronic inflammation at the greater curvature of the body increased with the extension of atrophic gastritis. In H. pylori-negative patients, the severity of chronic inflammation at the greater curvature of the body was significantly higher in patients with extensive atrophic gastritis than in those with a lesser extent of atrophic gastritis. CONCLUSION: At the greater curvature of the body, the development of atrophy is closely associated with the increase in the severity of inflammation, which is more marked in H. pylori-positive patients.

Adolescent↗
PubMed1996

Effect of some sulfonate analogues of ursodeoxycholic acid on biliary lipid secretion in the rat.

The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (norUDC-SO3Na) and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate (UDC-SO3Na), on biliary lipid secretion was studied in bile fistula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-dependent manner. This suggests that the analogues exert an effect on biliary lipid secretion comparable to that of the naturally occurring bile acid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates but greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC-SO3Na induced cholesterol secretion and phospholipid secretion more significantly than UDC-tau infusion. The increase in phospholipid secretion was particularly pronounced during high-dose administration of norUDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phospholipid output, perhaps as a compensatory mechanism, and the biliary cholesterol/phospholipid ratio was decreased to a greater extent by the sulfonates than by UDC-tau. Consequently, the administration of norUDC-SO3Na or UDC-SO3Na produces a more "stable" bile than UDC-tau, suggesting that these sulfonates possess potential cholelitholytic activity.

Animals↗
PubMed1996

15 alpha-hydroxylation of a bile acid analogue, sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate in the hamster.

The metabolism of 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul), the sulfonate analogue of bishomochenodeoxycholic acid, and its effect on biliary bile acid composition were studied during chronic administration in the hamster. After oral administration of radiolabeled bishomoCDC-sul, more than 80% of the radioactivity was excreted into the feces within 7 days, both as the unchanged sulfonate (38.5%) and two more polar metabolites (50.0% and 11.5%). The half time of the fecal excretion was 1.6 days. In gallbladder bile, the unchanged sulfonate and its major metabolite accounted for 19.1% and 19.8% of total bile acids, respectively. In another experiment, hamsters were fed bishomoCDC-sul with antibiotics to evaluate the site of biotransformation. Even when the number of intestinal microorganisms was greatly reduced, the same three metabolites were found in the feces: bishomoCDC-sul (44.0%) and the two polar metabolites (30.8% and 25.1%). The major metabolite was isolated from feces of the hamsters fed bishomoCDC-sul without antibiotics. Its chemical structure was identified by mass spectrometry and nuclear magnetic resonance spectroscopy as the 15 alpha-hydroxylated derivative, namely sodium 3 alpha,7 alpha,15 alpha-trihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate. These results indicate that after oral administration, the sulfonate analogue of bishomochenodeoxycholic acid underwent enterohepatic circulation like a natural bile acid and was transformed, in part, into the 15 alpha-hydroxylated derivative and another more polar metabolite in the liver of hamsters. There was no evidence that bishomoCDC-sul was dehydroxylated to a lithocholic acid analogue during enterohepatic cycling.

Animals↗
PubMed1996

Early recognition of patients with decreased methotrexate clearance following high-dose methotrexate infusion therapy.

The purpose of this study was to identify the patients with decreased methotrexate (MTX) clearance as early as possible after the start of high-dose methotrexate (HD-MTX) infusion. Fifty-six patients (age: 18 approximately 83 years) received a HD-MTX infusion (dosage: 1.9 approximately 3.8 g/m2) for 6 h. These patients were retrospectively divided into a low-clearance group and a high-clearance group based on the serum MTX concentration at 48 h (1 microM). Six out of the 56 patients showed decreased MTX clearance. The MTX concentrations in the low-clearance group were significantly higher than those in the high-clearance group even in earlier sampling times than at 48 h. The average MTX concentrations were 330 microM at 6 h, 72 microM at 12 h, and 16 microM at 24 h in the low-clearance group, and those in the high-clearance group were 210 microM, 18 microM, and 1.0 microM, respectively. The estimated elimination half-lives (t1/2) at 6 approximately 12 h and 12 approximately 24 h after the start of the infusion were also significantly longer in the low-clearance group (2.8 vs. 1.7 h and 5.0 vs. 2.8 h, respectively). Therefore, we proposed convenient criteria based on the mean + 1 S.D. of the high-clearance group: the concentration > 270 microM at 6 h and > 32 microM at 12 h; the t1/2 value > 2.1 h at 6-12 h. All 6 patients were recognized as belonging to the low-clearance group at an early stage after HD-MTX infusion by using our proposed criteria. These results indicate that patients with decreased MTX clearance could be identified within the first 12 h after the start of HD-MTX infusion. The factors influencing the prolonged elimination of MTX were also investigated. A significant decrease in renal function on day 2 was observed in the low-clearance group. The MTX level at 12 h and the estimated t1/2 values were significantly correlated with BUN, Scr and Clcr on the 2nd day after HD-MTX therapy, suggesting that an alteration in renal function occurs within 12 h of the HD-MTX infusion. The prolonged elimination of MTX could be attributable to this decrease in renal function.

Adult↗
PubMed1996

Simple 13C-urea breath test with infra-red spectrophotometer.

When mass spectrophotometric analysis is used for the 13C-urea breath test to assess H. pylori infection, it is costly, complicated, and time-consuming. To overcome these disadvantages, we utilized an infra-red spectrophotometer as a substitute for the mass spectrophotometer. A total of 153 patients (181 tests) analyzed with peptic ulcers or non-ulcer dyspepsia were investigated. Breath samples were collected 15 min after ingestion of 13C-urea (100 mg in 30 ml water). An infra-red spectrophotometer was used to determine the concentration of 13CO2 in the expirate. The 13CO2/12CO2 ratio was also measured by mass spectrophotometry to compare results with those of infra-red spectrophotometric analysis. Direct detection of H. pylori was qualified in biopsy specimens. Of the 181 biopsies, 138 were positive for H. pylori infection and 43 were negative. With the urea breath test, the mean value in the positive group was significantly higher than that in the negative group (0.062 +/- 0.044 vs 0.011 +/- 0.014, respectively). The cut-off level, 0.01, was determined as delta 13C atom %. The sensitivity of infra-red spectrophotometry was 97.8% (135/138) and specificity was 74.4% (32/43). There was an extremely high coefficient of correlation (r = 0.996) between mass and infra-red photometric analysis. Infra-red spectrometry appears to have great potential not only for diagnosing H. pylori infection but also for assessing treatment results. Its advantages include technical simplicity, cost-effectiveness, and high accuracy.

Breath Tests↗
PubMed1996

Efficacy of clarithromycin in eradicating Helicobacter pylori.

We reviewed reports on the efficacy of clarithromycin in eradicating Helicobacter pylori. Reports on dual and 1-week triple therapy that included clarithromycin were analyzed to assess the eradication rates of H. pylori infection. Dual therapy with clarithromycin and a proton pump inhibitor achieved eradication rates of 38%-83%, and 1-week triple therapy with omeprazole, clarithromycin, and other antibiotics achieved eradication rates, of 80%-96%. The incidence of side effects with all regimens was low. Clarithromycin is useful for treatment of H. pylori infection. One-week triple therapy that includes clarithromycin and a proton pump inhibitor effectively eradicates H. pylori.

Anti-Bacterial Agents↗