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1.
Pharmazie ; 63(1): 81-5, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18271310

ABSTRACT

The clinical significance of a proper eye drop application technique was evaluated in Japanese glaucoma patients. Patients diagnosed with primary open-angle glaucoma having intraocular pressure (IOP) greater than 21 mmHg were treated with eye drops at home. In some patients, however, the topical treatment was ineffective. They returned to the hospital to receive surgical treatment. On admission, 56% of these patients had IOP greater than 21 mmHg. Patient instillation technique was evaluated based on the proximity of the eyedropper tip to the eyes, application position, eyelid closure, treatment (removal) of excess fluid, and nasolacrimal occlusion. In addition, pharmacists interviewed patients to determine the level of understanding of glaucoma, knowledge of prescribed drugs, home application technique, and sensation after application. Multivariate analysis revealed that the key factors influencing the control of IOP to less than 21 mmHg with topical medication were: application of drops in the center of the eye and removal of excessive fluid, in addition to gender and age. Proper topical application at home was dependent on the patient's understanding of the disease, knowledge of prescribed drugs, patient education on the use of drugs, the competence of the instructor, and knowledge of correct application technique. This study indicates that easily comprehensible patient education on the use of eye drops, the nature of glaucoma and the proper use of prescribed drugs is vital to improving the clinical efficacy of topical ophthalmic medication of glaucoma in adult patients.


Subject(s)
Glaucoma/drug therapy , Ophthalmic Solutions/administration & dosage , Ophthalmic Solutions/therapeutic use , Administration, Topical , Adult , Aged , Female , Glaucoma/diagnosis , Humans , Intraocular Pressure , Male , Middle Aged , Multivariate Analysis , Ophthalmic Solutions/adverse effects , Pharmacists
2.
Clin Pharmacol Ther ; 81(4): 567-72, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17375106

ABSTRACT

Aldehyde oxidase (AO) plays an important role in metabolizing many drugs, so AO activity in individual patients may be a useful parameter for dose adjustment to avoid severe toxicity. In this study, we investigated the developmental changes of AO activity in 101 children. Urine was collected in the morning, and AO activity was assessed in terms of the ratio of pyridone formation from N(1)-methylnicotinamide, an AO substrate. Significant correlations were found between AO activity and various growth indices (age, body weight, body surface area, and liver volume). Age showed the moderate correlation (r(2)=0.506). AO activity rapidly increased with increase of the subjects' age up to about 1 year. These findings suggest that the AO activity begins to increase soon after birth. Because AO activity is immature in children below 1 year of age, dose adjustment based on individual AO activity should be made for such patients.


Subject(s)
Aging/metabolism , Aldehyde Oxidase/metabolism , Body Surface Area , Child , Child, Preschool , Female , Humans , Infant , Liver/enzymology , Male , Niacinamide/pharmacokinetics , Pyridones/metabolism , Sex Characteristics , Twins, Monozygotic
3.
J Inherit Metab Dis ; 27(6): 787-8, 2004.
Article in English | MEDLINE | ID: mdl-15617192

ABSTRACT

We describe the results of mutational analysis of the carbamoylphosphate synthetase I (CPSI) gene in three nonconsanguineous patients with CPSI deficiency. Compound heterozygotes of 3422T/G (V1141G) plus 3784C/T (R1262X), 1528delG (510-514 ARQLX) plus 2752T/C (S918P), and 2549G/A (R850H) plus 2797delT (L933X) were identified through genomic analysis; however, the 2797delT (L933X) mutation was not detected in cDNA analysis using biopsied liver, suggesting that mRNA expression rom this mutant allele is absent or markedly low.


Subject(s)
Carbamoyl-Phosphate Synthase (Ammonia)/genetics , Carbamoyl-Phosphate Synthase I Deficiency Disease/genetics , Adolescent , DNA Mutational Analysis , DNA, Complementary/genetics , Female , Heterozygote , Humans , Infant, Newborn , Japan , Liver/metabolism , Liver/pathology , Male , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction
4.
Scand J Gastroenterol ; 38(5): 482-90, 2003 May.
Article in English | MEDLINE | ID: mdl-12795457

ABSTRACT

BACKGROUND: As a consequence of gastric histological differences, Japanese and Swedish peptic ulcer (PU) patients may respond differently to Helicobacter pylori eradication therapies. METHODS: The study was single-blind and compared four eradication therapies in Japanese and Swedish patients with healed gastric (GU) or duodenal (DU) ulcer. Swedish patients received either (a) omeprazole+clarithromycin (OC, where O = 20 mg, C = 500 mg) for 2 weeks, or triple therapy with (b) omeprazole + amoxicillin + clarithromycin (OAC-L where O = 20mg, A = 1 g, C = 250 mg); (c) OAC-H (where O = 20 mg, A-1 g, C-500 mg); or (d) omeprazole + metronidazole + clarithromycin (OMC, where O = 20 mg, M = 400 mg, C = 250 mg) for 1 week. Antibiotic doses were weight-adjusted downwards in Japanese patients. H. pylori was assessed using the urea breath test (UBT), histology and culture pre-entry, with UBT being repeated 4 and 8 weeks after stopping treatment. Histology and culture were repeated if the UBT was positive post-therapy. RESULTS: Recruitment included 120 patients from Japan (43 GU, 61 DU, 16 GU+DU) and 120 from Sweden (119 DU, 1 GU+DU). There were 26 exclusions from a FAS analysis due to H. pylori negativity (14), no drug administration (7) or no data after visit 1 (5). Eradication rates (FAS) from Japan were (a) 63%, (b) 93%, (c) 96% or (d) 96%, and for Sweden (a) 92%, (b) 86%, (c) 93% or (d) 96%. Dual therapy was less effective in patients with gastric atrophy associated with GU disease. Tolerability was good in all treatment groups, with no serious adverse events. CONCLUSION: Triple therapies were safe and effective for H. pylori eradication in Japanese and Swedish peptic ulcer patients. Dual therapy was significantly less effective in the Japanese patients, half of whom had a history of GU and more abnormal histology than in the Swedish patients, all of whom had DU.


Subject(s)
Helicobacter Infections/drug therapy , Helicobacter pylori , Peptic Ulcer/drug therapy , Peptic Ulcer/ethnology , Adult , Aged , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Asian People , Clarithromycin/therapeutic use , Drug Therapy, Combination , Female , Helicobacter Infections/complications , Humans , Japan , Male , Metronidazole/therapeutic use , Middle Aged , Omeprazole/therapeutic use , Peptic Ulcer/microbiology , Sweden , White People
5.
Scand J Gastroenterol ; 38(5): 491-7, 2003 May.
Article in English | MEDLINE | ID: mdl-12795458

ABSTRACT

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.


Subject(s)
Gastric Mucosa/pathology , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections/complications , Helicobacter pylori , Peptic Ulcer/microbiology , Stomach/pathology , Adult , Aged , Biopsy , Female , Gastritis/physiopathology , Humans , Japan , Male , Middle Aged , Peptic Ulcer/pathology , Sweden
6.
Dig Liver Dis ; 35(2): 78-84, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12747624

ABSTRACT

BACKGROUND: Change in apoptosis in gastric glands after eradication of Helicobacter pylori has never been reported. AIMS: The purpose of this paper is to investigate the change in apoptosis in gastric glands after eradication of Heliobacter pylori. PATIENTS AND METHODS: We studied 23 Heliobacter pylori-positive patients with duodenal and gastric ulcers, who were monitored for 6-12 months after eradication, and eight controls. Biopsies were taken from the antrum and body. Apoptosis was evaluated immunohistochemically using anti-single stranded DNA antibody. Apoptotic index was calculated by counting immunostained cells in surface epithelial and glandular cells. RESULTS: In the surface epithelium, Apoptotic indexes were significantly higher in patients than in controls. In the upper portion of fundic glands, apoptotic indexes were significantly higher in patients with gastric ulcers (14.2% (9.3, 17.8)) (median (1st quartile, 3rd quartile)) than in controls (8.0% (2.0, 9.0), p < 0.01) and decreased significantly after eradication (3.4% (2.0, 5.3)), p < 0.01). In pyloric glands, apoptotic indexes were no different between patients and controls. In the lower portion of fundic glands, apoptotic indexes were very low, both in patients and in controls. CONCLUSIONS: Our results showed that apoptosis, not only of surface epithelial cells but also of glandular cells in the upper portion of fundic glands, increased in Heliobacter pylori-positive patients with gastric ulcers and decreased to normal levels after eradication of Heliobacter pylori.


Subject(s)
Apoptosis , Gastric Mucosa/pathology , Helicobacter Infections/drug therapy , Helicobacter pylori , Stomach Ulcer/drug therapy , Adult , Aged , DNA, Single-Stranded/analysis , Epithelium/pathology , Female , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections/pathology , Humans , Immunohistochemistry , Male , Middle Aged , Stomach Ulcer/microbiology , Stomach Ulcer/pathology
7.
Scand J Gastroenterol ; 38(5): 491-497, 2003.
Article in English | MEDLINE | ID: mdl-28443767

ABSTRACT

BACKGROUND: The natural course of Helicobacter pylori gastritis may vary between different ethnic groups. Gastric histopathology and the occurrence of H. pylori organisms in the stomach were investigated in healed duodenal (DU) and gastric (GU) ulcer patients recruited in Sweden (S) and Japan (J) in an identical trial. METHODS: In 203 patients (JGU = 39, JDU = 55, SDU = 109), various morphological gastritis variables and H. pylori were assessed from biopsy specimens obtained using a specific sampling protocol and interpreted according to guidelines of the updated Sydney grading system. RESULTS: The ratio of GU:DU was observed to be very different between the recruited Japanese (39:55) and Swedish (0:109) patients. A comparison of data from SDU and JDU showed that the prevalence of H. pylori infection and the antral predominant gastritis demonstrated by both SDU and JDU were essentially identical. A comparison of data from JDU and JGU demonstrated a greater prevalence of H. pylori infection in the antrum, but not corpus, of JDU compared to JGU patients. The prevalence of atrophy and intestinal metaplasia was higher in both the antrum and corpus of JGU compared to JDU in all patients. CONCLUSIONS: The site specified biopsy methodology and standardized interpretation criteria utilized in this study clearly show that the histotopographic profile of Swedish and Japanese DU patients is essentially the same.

8.
Yakugaku Zasshi ; 121(11): 799-806, 2001 Nov.
Article in Japanese | MEDLINE | ID: mdl-11725548

ABSTRACT

In this study, factors influencing patients adherence to ophthalmic solutions were investigated. Seventy-one subjects (aged 62.3 +/- 15.5 years) were randomly selected from patients admitted to the Ophthalmology Department at Hiroshima University Hospital. The patients (n = 71) completed questionnaires, which were evaluated by clinical pharmacists. The patient group to which the ophthalmic solutions were applied once or twice daily was more compliant than other patient groups (p = 0.00057). A multivariate statistical analysis revealed that the factors influencing patients adherence were the number of ophthalmic solutions used, patient age, taste, administration intervals, the number of drops used, and hand washing before the application of ophthalmic solutions. Patients who understood the significance of the medication made fewer mistakes than those who understood only the route of administration but not the significance. In conclusion, our study shows that patient counseling should emphasis the significance of the administered medicine as well as the route of administration.


Subject(s)
Ophthalmic Solutions/administration & dosage , Patient Compliance/statistics & numerical data , Aged , Female , Humans , Male , Middle Aged , Multivariate Analysis , Patient Education as Topic , Random Allocation , Surveys and Questionnaires
9.
Gan To Kagaku Ryoho ; 28(11): 1498-500, 2001 Oct.
Article in Japanese | MEDLINE | ID: mdl-11707963

ABSTRACT

This study was performed to evaluate the feasibility and clinical impact of intraluminal and endovascular high-dose-rate iridium-192 brachytherapy on the treatment of HCC lesions growing into biliary trees, portal veins and the inferior vena cava. HCCs involving biliary trees in 2 patients, the main and/or first-order portal veins in 3 patients, and the inferior vena cava in 2 patients. Brachytherapy was percutaneously performed with a 5F applicator, which was placed adjacent to the lesions. A mean total dose of 23 Gy (range, 5-7 Gy/fr) was irradiated (at a 5 mm radius) to the biliary or the portal venous tumors. A total dose of 10 Gy (5 Gy/fr) was given to the caval tumors. External-beam radiotherapy was combined in 2 patients with caval lesions, stent placement in 2 patients with biliary lesions and hepatic arterial infusion chemotherapy in 5 patients. There was no major complication except hemobilia, which ceased after placing a PTCD tube in the bile duct in one patient. All tumors were significantly reduced in size and remained controlled during the period of patients' survival. Complete tumor necrosis was histologically proved in 2 autopsy cases having biliary lesions. The median survival was 13 months. Intraluminal and endovascular high-dose-rate brachytherapy appears to be a feasible, and effective procedure to treat advanced HCCs invading biliary trees, portal veins and the vena cava.


Subject(s)
Brachytherapy , Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Vascular Neoplasms/radiotherapy , Aged , Biliary Tract/pathology , Brachytherapy/standards , Carcinoma, Hepatocellular/pathology , Feasibility Studies , Female , Humans , Iridium Radioisotopes/administration & dosage , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Portal Vein/pathology , Radiotherapy Dosage , Vascular Neoplasms/pathology , Venae Cavae/pathology
10.
Gastrointest Endosc ; 54(5): 629-32, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11677485

ABSTRACT

BACKGROUND: The advisability of endoscopic mucosal resection (EMR) for treatment of large superficial gastric cancers has been challenged. For more reliable en bloc resection, a new method of EMR was developed that uses a viscous substance, sodium hyaluronate, and two newly designed devices. METHODS: A large superficial gastric cancer was treated with this new EMR technique. Sodium hyaluronate was injected into the submucosa and mucosal incisions were made with a needle-knife. The newly developed incision forceps and flat-ended transparent hood were used for submucosal incisions. RESULTS: The large cancer was successfully resected endoscopically as a single piece of mucosa 6 cm in diameter without complication. Histopathologic evaluation of the specimen confirmed that the resection was curative. CONCLUSIONS: EMR with sodium hyaluronate along with two new devices may be a reliable method for en bloc resection of large superficial gastric lesions.


Subject(s)
Electrocoagulation/instrumentation , Endoscopy, Gastrointestinal , Stomach Neoplasms/surgery , Aged , Humans , Hyaluronic Acid/administration & dosage , Male , Stomach Neoplasms/pathology
11.
Helicobacter ; 6(1): 31-6, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11328363

ABSTRACT

BACKGROUND: Accumulation of p53 has been recognized in the gastric mucosa infected with Helicobacter pylori. We investigated the prevalence of p53-positive cells in the gastric mucosa before and one month after eradication of H. pylori and the relationship between p53 positivity and inflammation and cell proliferation. METHODS: The subjects included 24 H. pylori-positive patients. They achieved eradication one month after anti-H. pylori therapy. Biopsies were taken from the greater curvatures of the antrum and middle body. H. pylori status was assessed using culture and tissue section (Giemsa stain). Serial sections were used for examination of gastritis (hematoxylin and eosin stain) and for immunostaining of p53, Ki-67 and myeloperoxidase (MPO). p53 index and Ki-67 labeling index (LI) were calculated by counting p53-positive and Ki-67-positive cells in the entire gastric pits longitudinally sectioned and expressing them as a percentage of the total cells in a gastric pit. In the neck regions with and without p53-positive cells, polymorphonuclear leukocytes (PMNs) were counted in the corresponding area (/50 x 50 microm2) of the sections stained both with p53 and MPO. RESULTS: p53-positive cells decreased significantly after eradication of H. pylori. Before eradication, the number of PMNs was significantly higher in the neck regions with p53-positive cells than in those without. CONCLUSIONS: In the gastric mucosa infected with H. pylori, p53-positive cells were found in the neck region infiltrated with PMNs. p53 expression decreased significantly one month after eradication of H. pylori.


Subject(s)
Gastric Mucosa/pathology , Helicobacter Infections/metabolism , Helicobacter pylori , Tumor Suppressor Protein p53/metabolism , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Biopsy , Cell Division , Female , Gastric Mucosa/microbiology , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Humans , Immunohistochemistry , Ki-67 Antigen/analysis , Male , Middle Aged , Neutrophils/pathology , Peroxidase/analysis , Pyloric Antrum/microbiology , Pyloric Antrum/pathology
12.
Jpn J Ophthalmol ; 45(1): 99-102, 2001.
Article in English | MEDLINE | ID: mdl-11163052

ABSTRACT

PURPOSE: We conducted a study of the daily cost of various ophthalmic solutions used in Japan for treating glaucoma: beta-adrenergic blockers (11 products), epinephrine (3), cholinergics (3), prostaglandins (2), and carbonic anhydrase inhibitors (2). METHODS: The total number of drops in one bottle of each solution was counted drop by drop. The cost per drop was calculated by dividing the government-controlled standard prices by the total number of drops in one bottle. The daily cost of therapy was calculated by multiplying the cost per drop by the number of drops typically used per day. RESULTS: The average cost of each preparation was calculated based on the prices and the daily usage. The daily cost of the beta-adrenergic blockers studied ranged widely, from $0.43 to $1.04. CONCLUSIONS: These data may be useful in selecting ophthalmic products for glaucoma therapy in Japan.


Subject(s)
Drug Costs , Glaucoma/economics , Ophthalmic Solutions/economics , Adrenergic Agonists/economics , Adrenergic Agonists/therapeutic use , Adrenergic beta-Antagonists/economics , Adrenergic beta-Antagonists/therapeutic use , Carbonic Anhydrase Inhibitors/economics , Carbonic Anhydrase Inhibitors/therapeutic use , Cholinergic Agents/economics , Cholinergic Agents/therapeutic use , Glaucoma/drug therapy , Humans , Japan , Ophthalmic Solutions/therapeutic use , Prostaglandins/economics , Prostaglandins/therapeutic use
13.
J Lipid Res ; 41(10): 1562-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11013297

ABSTRACT

The stereochemistry at C-24 and C-25 of 27-nor-5beta-cholestane-3alpha,7alpha,12alpha,24 ,25-pentol, a principal bile alcohol in human urine, and its biosynthesis are studied. Four stereoisomers of the C(26)-24,25-pentols were synthesized by reduction with LiAlH(4) of the corresponding epoxides prepared from (24S)- or (24R)-27-nor-5beta-cholest-25-ene-3alpha, 7alpha,12alpha,24-tetrol. The stereochemistries at C-25 were deduced by comparison of the C(26)-24,25-pentols with the oxidation products of (24Z)-27-nor-5beta-cholest-24-ene-3alpha,7alpha, 12alpha-triol with osmium tetraoxide. On the basis of this assignment, the principal bile alcohol excreted into human and rat urine was determined to be (24S,25R)-27-nor-5beta-cholestane-3alpha,7alpha, 12alpha,24,25-pentol, accompanied by a lesser amount of (24R, 25R)-isomer. To elucidate the biosynthesis of the C(26)-24,25-pentol, a putative intermediate, 3alpha,7alpha, 12alpha-trihydroxy-27-nor-5beta-cholestan-24-one, derived from 3alpha,7alpha, 12alpha-trihydroxy-24-oxo-5beta-cholestanoic acid by decarboxylation during the side-chain oxidation of 3alpha,7alpha, 12alpha-trihydroxy-5beta-cholestanoic acid, was incubated with rat liver homogenates. The 24-oxo-bile alcohol could be efficiently reduced to yield mainly (24R)-27-nor-5beta-cholestane-3alpha,7alpha, 12alpha,24-tetrol. If a 25R-hydroxylation of the latter steroid occurs, it should lead to formation of (24S,25R)-C(26)-24,25-pentol. Now it has appeared that a major bile alcohol excreted into human urine is (24S,25R)-27-nor-5beta-cholestane-3alpha,7alpha, 12alpha, 24, 25-pentol, which might be derived from 3alpha,7alpha, 12alpha-trihydroxy-27-nor-5beta-cholestan-24-one via (24R)-27-nor-5beta-cholestane-3alpha, 7alpha,12alpha,24-tetrol.


Subject(s)
Cholestanols/chemistry , Cholestanols/urine , Animals , Carbon Isotopes , Cholestanols/chemical synthesis , Cholic Acid/chemistry , Chromatography, Gas , Chromatography, Thin Layer , Humans , Liver/chemistry , Male , Rats , Rats, Wistar , Reference Standards , Stereoisomerism
14.
Aliment Pharmacol Ther ; 14(8): 1083-7, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10930904

ABSTRACT

BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of 100 subjects with H. pylori were randomly divided into two groups of 1-week triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800, n=50). Endoscopic examination with four biopsies (two specimens from the antrum and two from the gastric body) was performed. The status of H. pylori infection was determined using culture and histology (Giemsa stain) of the biopsy specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8 g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be sensitive. Cure was defined as no evidence of H. pylori infection 1 month after completion of treatment. RESULTS: There were no significant differences in the clinical characteristics of the two groups. Eradication rates (intention-to-treat and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95% CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was no significant difference between the eradication rates of either regimen. Three subjects with failed eradication in the RAC400 group were all infected with a clarithromycin-resistant strain before beginning the therapy. Haemorrhagic colitis was the only severe adverse event, which was observed in one patient in the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole, amoxycillin and low-dose clarithromycin is effective for the eradication of H. pylori infection.


Subject(s)
Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Ulcer Agents/administration & dosage , Benzimidazoles/administration & dosage , Clarithromycin/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Penicillins/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Aged , Amoxicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/therapeutic use , Benzimidazoles/therapeutic use , Clarithromycin/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Helicobacter Infections/pathology , Humans , Male , Middle Aged , Omeprazole/analogs & derivatives , Penicillins/therapeutic use , Rabeprazole , Treatment Outcome
15.
Brain Res ; 834(1-2): 6-12, 1999 Jul 10.
Article in English | MEDLINE | ID: mdl-10407088

ABSTRACT

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.


Subject(s)
Amnesia/chemically induced , Biperiden/metabolism , Brain/metabolism , Cholinergic Antagonists/metabolism , Receptors, Muscarinic/metabolism , Trihexyphenidyl/metabolism , Animals , Avoidance Learning/drug effects , Binding, Competitive , Biperiden/pharmacology , Cerebral Cortex/metabolism , Cholinergic Antagonists/pharmacology , Electroshock , Male , Membranes/metabolism , Pain/physiopathology , Quinuclidinyl Benzilate/metabolism , Rats , Rats, Wistar , Retention, Psychology/drug effects , Time Factors , Trihexyphenidyl/pharmacology
16.
Helicobacter ; 4(1): 1-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10352081

ABSTRACT

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.


Subject(s)
Antigens, Bacterial , Bacterial Proteins/genetics , Helicobacter Infections/microbiology , Helicobacter pylori/genetics , Helicobacter pylori/pathogenicity , Peptic Ulcer/diagnosis , Peptic Ulcer/microbiology , Adolescent , Adult , Aged , Bacterial Proteins/pharmacology , Biomarkers/analysis , Biopsy , Cell Division/drug effects , Child , Chronic Disease , Cytotoxins/genetics , Cytotoxins/pharmacology , DNA, Bacterial/genetics , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/diagnosis , Gastritis/microbiology , Gene Frequency , Helicobacter Infections/complications , Helicobacter Infections/diagnosis , Helicobacter pylori/classification , Humans , Male , Middle Aged , Species Specificity
18.
Nihon Rinsho ; 57(1): 148-52, 1999 Jan.
Article in Japanese | MEDLINE | ID: mdl-10036953

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Ulcer Agents/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori , Histamine H2 Antagonists/administration & dosage , Peptic Ulcer/drug therapy , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Aged , Aged, 80 and over , Clarithromycin/administration & dosage , Double-Blind Method , Drug Evaluation , Drug Therapy, Combination , Female , Helicobacter Infections/microbiology , Humans , Lansoprazole , Male , Metronidazole/administration & dosage , Middle Aged , Omeprazole/administration & dosage , Omeprazole/analogs & derivatives , Peptic Ulcer/microbiology , Proton Pump Inhibitors , Ranitidine/administration & dosage , Treatment Outcome
19.
Nihon Rinsho ; 57(1): 185-90, 1999 Jan.
Article in Japanese | MEDLINE | ID: mdl-10036960

ABSTRACT

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.


Subject(s)
Gastritis, Atrophic/microbiology , Gastritis, Atrophic/pathology , Helicobacter Infections , Helicobacter pylori , Follow-Up Studies , Gastric Mucosa/pathology , Humans , Severity of Illness Index
20.
Helicobacter ; 3(4): 236-40, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9844064

ABSTRACT

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.


Subject(s)
Gastritis, Atrophic/microbiology , Gastritis, Atrophic/pathology , Helicobacter pylori , Intestines/pathology , Adult , Atrophy , Female , Follow-Up Studies , Gastritis, Atrophic/drug therapy , Humans , Male , Metaplasia , Middle Aged
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