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1.
Oncotarget ; 11(19): 1705-1713, 2020 May 12.
Article in English | MEDLINE | ID: mdl-32477460

ABSTRACT

INTRODUCTION: Lower handgrip strength is a manifestation of sarcopenia and frailty, and has been reported to be associated with cerebral microbleeds (CMBs), which appear on T2*-weighted magnetic resonance scans as low-intensity spots. However, the underlying mechanism is unknown. We hypothesized that vascular endothelial injury could be the common factor in loss of handgrip strength and CMBs. We aimed to clarify the relationship between handgrip strength and CMBs, with reference to a marker of vascular repair capability. MATERIALS AND METHODS: We conducted a cross-sectional study of 95 60- to 87-year-old Japanese people who underwent brain magnetic resonance imaging in 2016-2017. Baseline information was obtained by trained interviewers regarding the age, sex, smoking status, nutrient intake, cognition, medical history, education, and household income of the participants. Physical activity was assessed using a tri-axial accelerometer. We used the Fried frailty phenotype definition. Multivariable linear regression analysis was performed. RESULTS: Handgrip strength was independently associated with the presence of CMB after adjustment for age, sex, body mass index, classical cardiovascular risk factors, protein intake, and daily activity (B = -3.43, p = 0.027). This association was shown in participants with a low (B = -4.05, p = 0.045) but not high platelet count (B=-2.23, p = 0.479). Frailty was also independently associated with the presence of CMB after adjustment for confounders (B = 0.57, p = 0.014). Although this association was not present in participants a high platelet count, there was a positive trend in those with a low platelet count (B = 0.50, p = 0.135). CONCLUSIONS: Platelet count, a marker of vascular repair capability, appears to modify the relationship between handgrip strength and CMBs.

2.
BMJ Case Rep ; 20182018 Jan 04.
Article in English | MEDLINE | ID: mdl-29301814

ABSTRACT

Strongyloides stercoralis infection is a common and neglected public health problem in many areas of the world. Here we report the case of a 21-year-old woman who emigrated from Cambodia to Japan and presented with swelling of the right supraclavicular region of 2 months' duration. She had no other symptoms. Tuberculous lymphadenitis was diagnosed based on a fine-needle aspiration biopsy of the right supraclavicular lymph node. The laboratory examination revealed mild eosinophilia (eosinophils 1348/µL).S. stercoralis and Hymenolepis nana were detected serologically and in faeces examination. This case demonstrates that clinicians should search for S. stercoralis infection in patients with tuberculosis who have epidemiological risk factors and/or laboratory signs of eosinophilia, even if other symptoms and signs of helminths infection are less obvious.


Subject(s)
Eosinophilia/parasitology , Strongyloidiasis/diagnosis , Tuberculosis, Lymph Node/parasitology , Asymptomatic Infections , Female , Humans , Strongyloidiasis/parasitology , Young Adult
4.
Case Rep Med ; 2015: 968152, 2015.
Article in English | MEDLINE | ID: mdl-26229538

ABSTRACT

Introduction. Family physicians have more opportunities to attend athletic competitions as medical staff at first-aid centers because of the increasing popularity of endurance sports. Case. A 38-year-old man who participated in a triathlon race experienced difficulty in breathing after swimming and was moved to a first-aid center. His initial oxygen saturation was 82% and a thoracic computed tomography scan showed bilateral ground glass opacity in the peripheral lungs. His diagnosis was noncardiogenic pulmonary edema associated with exercise or swimming: exercise-induced pulmonary edema (EIPE) or swimming-induced pulmonary edema (SIPE). Treatment with furosemide and corticosteroid relieved his symptoms of pulmonary edema. Discussion. Noncardiogenic pulmonary edema associated with endurance sports is not common, but knowledge about EIPE/SIPE or neurogenic pulmonary edema associated with hyponatremia, which is called Ayus-Arieff syndrome, is crucial. Knowledge and caution for possible risk factors, such as exposure to cold water or overhydration, are essential for both medical staff and endurance athletes. Conclusion. To determine the presence of pulmonary edema associated with strenuous exercise, oxygen saturation should be used as a screening tool at a first-aid center. To avoid risks for EIPE/SIPE, knowledge about these diseases is essential for medical staff and for athletes who perform extreme exercise.

5.
Intern Med ; 46(12): 839-44, 2007.
Article in English | MEDLINE | ID: mdl-17575375

ABSTRACT

OBJECT: Anemia and leukopenia caused by copper deficiency are well-documented consequences of long-term total parenteral nutrition. We measured the serum copper levels of bed-ridden patients receiving enteral feeding, and evaluated optical and ultrastructural features of bone marrow before and after copper supplementation. PATIENTS AND METHODS: Serum samples were obtained from 15 bed-ridden elderly patients receiving tube feeding (TF) and 10 age-matched bed-ridden patients who took food orally (CO), and the copper ceruloplasmin concentration of each sample was measured. Bone marrow samples were obtained from patients who exhibited copper deficiency and leukopenia and/or anemia before and after the copper supplementation, for use in light and electron microscopic analysis. RESULTS: The tube-fed patients had significantly lower mean serum copper and ceruloplasmin concentrations than the control patients. Seven of the 15 tube-fed patients had reduced serum copper concentrations and leukopenia. Six of those 7 patients also had anemia. Copper sulfate was administered to those 7 patients by enteral tube; their copper concentration, anemia and leukopenia improved within 1 month after they were administered copper sulfate. In the bone marrow examination before copper supplementation, light microscopy showed cytoplasmic vacuolization in both myeloid and erythroid precursors, and electron microscopy showed electron-dense deposits in mitochondria and cytoplasm of erythroid and myeloid cells. After copper supplementation, these pathological changes disappeared. CONCLUSIONS: Bicytopenia is likely to occur in tube-fed patients with copper deficiency. Copper deficiency appears to be associated with cytoplasmic vacuolization and electron-dense deposits in mitochondria in erythroid and myeloid cells.


Subject(s)
Anemia/etiology , Copper/deficiency , Deficiency Diseases/complications , Enteral Nutrition , Leukopenia/etiology , Aged , Aged, 80 and over , Anemia/blood , Anemia/diet therapy , Bone Marrow/drug effects , Bone Marrow/pathology , Ceruloplasmin/drug effects , Ceruloplasmin/metabolism , Copper/administration & dosage , Copper/blood , Deficiency Diseases/pathology , Dietary Supplements , Female , Humans , Leukopenia/blood , Leukopenia/diet therapy , Male , Reference Values , Treatment Outcome
6.
World J Gastroenterol ; 11(31): 4833-7, 2005 Aug 21.
Article in English | MEDLINE | ID: mdl-16097053

ABSTRACT

AIM: To investigate the frequency and distribution of N-acetyltransferase 2 (NAT2) and uridine 5'-diphosphate (UDP)-glucuronosyltransferase 1A7 (UGT1A7) genes in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: Frequencies and distributions of NAT2 and UGT1A7 SNPs as well as their haplotypes were investigated in 95 patients with UC, 60 patients with CD, and 200 gender-matched, unrelated, healthy, control volunteers by PCR-restriction fragment length polymorphism (RFLP), PCR-denaturing high-performance liquid chromatography (DHPLC), and direct DNA sequencing. RESULTS: Multiple logistic regression analysis revealed that the frequency of haplotype, NAT2*7B, significantly increased in CD patients, compared to that in controls (P = 0.0130, OR = 2.802, 95%CI = 1.243-6.316). However, there was no association between NAT2 haplotypes and UC, or between any UGT1A7 haplotypes and inflammatory bowel disease (IBD). CONCLUSION: It is likely that the NAT2 gene is one of the determinants for CD in Japanese. Alternatively, a new CD determinant may exist in the 8p22 region, where NAT2 is located.


Subject(s)
Arylamine N-Acetyltransferase/genetics , Colitis, Ulcerative/enzymology , Crohn Disease/enzymology , Crohn Disease/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Aged , Aged, 80 and over , Gene Frequency , Humans , Middle Aged , Reference Values
7.
Histochem Cell Biol ; 121(5): 399-405, 2004 May.
Article in English | MEDLINE | ID: mdl-15138841

ABSTRACT

Although estrogen is implicated in the regulation of mammalian intestinal function, the presence and the distribution of estrogen receptor (ER)-positive cells in the intestine are still controversial. The present study was designed to localize ERalpha- and ERbeta-expressing cells in female and male mouse intestines immunohistochemically under various estrogen conditions, especially in female mice, ovariectomized as well at various phases of the estrous cycle. Western blot analysis detected both ERalpha (66-kDa band) and ERbeta (56-kDa band). Immunohistochemical staining of paraffin-embedded sections after antigen-retrieval treatment with autoclaving revealed staining for ERalpha in submucosal interstitial cells, and double staining identified these cells as a subtype of intestinal macrophages. The number of these cells varied according to the estrous cycle phase. Administration of 17beta-estradiol to ovariectomized mice resulted in a significant increase in the number of ERalpha-positive macrophages. On the other hand, the nuclei of nerve cells in Auerbach and Meissner plexuses were positive for both ERalpha and ERbeta, but the number of positive nerve cells was not affected by estrogen. Our results indicate that estrogen and estrogenic compounds may exert their actions on the intestine in two ways; one is through interstitial macrophages and the other is through intestinal neurons.


Subject(s)
Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Estrogens/metabolism , Intestinal Mucosa/metabolism , Animals , Antigens, Differentiation/analysis , Blotting, Western , Diethylstilbestrol/pharmacology , Estradiol/pharmacology , Estrogen Receptor alpha/analysis , Estrogen Receptor beta/analysis , Estrogens/pharmacology , Estrous Cycle/metabolism , Female , Granulosa Cells/chemistry , Immunohistochemistry , Intestinal Mucosa/chemistry , Intestinal Mucosa/cytology , Intestine, Large/chemistry , Intestine, Large/drug effects , Intestine, Large/metabolism , Intestine, Small/chemistry , Intestine, Small/drug effects , Intestine, Small/metabolism , Intestines/chemistry , Intestines/drug effects , Macrophages/chemistry , Male , Mice , Mice, Inbred ICR , Myenteric Plexus/chemistry , Myenteric Plexus/cytology , Ovariectomy , Ovary/chemistry , Ovary/cytology , Sex Factors , Stromal Cells/chemistry , Submucous Plexus/chemistry , Submucous Plexus/cytology , Uterus/chemistry
8.
Int J Cancer ; 108(1): 146-51, 2004 Jan 01.
Article in English | MEDLINE | ID: mdl-14618629

ABSTRACT

Breast cancer resistance protein (BCRP/ABCG2) of an ATP-binding cassette half-transporter confers resistance against mitoxantrone and camptothecin derivatives of topotecan and irinotecan. Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro and in vivo, the mechanism of which remains undetermined. Here we focused on drug efflux pump and examined whether novobiocin reversed drug resistance in multidrug-resistant cells highly expressing BCRP. To explore the reversal mechanisms, intracellular drug accumulation was measured by flow cytometry, and a topotecan transport study using plasma membrane vesicles was performed. We used PC-6/SN2-5H2 small cell lung cancer and MCF-7/MX breast cancer cells selected with SN-38 of the active irinotecan metabolite and mitoxantrone, respectively, and the BCRP cDNA transfectant MCF-7/clone 8 cells. These cells expressed high levels of BCRP mRNA but not other known transporters. Compared to the parental PC-6 cells, PC-6/SN2-5H2 cells were 141-, 173- and 57.2-fold resistant to topotecan, SN-38 and mitoxantrone, respectively. Novobiocin at 60 microM decreased the degree of the above resistance by approximately 26-fold in PC-6/SN2-5H2 cells, and similarly reversed resistance in MCF-7/MX, MCF-7/clone 8 and un-selected NCI-H460 cells highly expressing BCRP. Furthermore, novobiocin increased the intracellular topotecan accumulation in these cells and inhibited the topotecan transport into the membrane vesicles of PC-6/SN2-5H2 cells. No effects of novobiocin in these assay were observed in the parental PC-6 and MCF-7 cells. The kinetic parameters in the transport study indicated that novobiocin was a inhibitor for BCRP, resulting in competitive inhibition of BCRP-mediated topotecan transport. These findings suggest that novobiocin effectively overcomes BCRP-mediated drug resistance at acceptable concentrations.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Breast Neoplasms/drug therapy , Camptothecin/analogs & derivatives , Drug Resistance, Neoplasm/drug effects , Neoplasm Proteins/metabolism , Novobiocin/pharmacology , ATP Binding Cassette Transporter, Subfamily G, Member 2 , ATP-Binding Cassette Transporters/antagonists & inhibitors , Aminocoumarins , Camptothecin/pharmacology , Coumarins/pharmacology , Drug Resistance, Multiple/drug effects , Humans , Irinotecan , Lung Neoplasms/drug therapy , Mitoxantrone/pharmacology , Neoplasm Proteins/antagonists & inhibitors , Topoisomerase I Inhibitors , Topotecan/metabolism , Topotecan/pharmacology , Tumor Cells, Cultured
9.
Dig Dis Sci ; 48(10): 2104-7, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14627362

ABSTRACT

Anemia is a common problem that results from various causes in patients with ulcerative colitis (UC), but there is little information on the association of UC with pure red cell aplasia (PRCA). We describe the first case of parvovirus-induced PRCA in UC. A 28-year-old woman with chronic UC was admitted to the hospital for treatment of active pancolitis. Three courses of pulse therapy with methylprednisolone provided complete remission. However, the patient developed reticulocytopenia and a subsequent fall in hemoglobin to 6.2 g/dl. Bone marrow examination revealed selective aplasia of red cell precursors and giant pronoromoblasts. Enzyme immunoassay identified specific immunoglobulin M antibody against parvovirus B19 in the serum. Based on these findings, the diagnosis of PRCA caused by the virus was made. The patient was treated with a 3-day course of intravenous immunoglobulin (5 g/day), resulting in brisk reticulocytosis, folowed by normalization of hemoglobin level. In conclusion, Chronic or acute blood loss in UC associated with enhanced red cell turnover might be a risk factor for PRCA when affected patients contract parvovirus B19 infection.


Subject(s)
Colitis, Ulcerative/complications , Parvoviridae Infections/complications , Parvovirus B19, Human , Red-Cell Aplasia, Pure/virology , Adult , Bone Marrow/pathology , Colitis, Ulcerative/pathology , Endoscopy, Digestive System , Female , Humans , Red-Cell Aplasia, Pure/pathology
11.
J Gastroenterol ; 38(9): 884-90, 2003.
Article in English | MEDLINE | ID: mdl-14564634

ABSTRACT

Extraintestinal manifestations of ulcerative colitis (UC) are well known, but immunologically mediated hematological diseases are relatively rare. We describe two cases of immune thrombocytopenic purpura (ITP) associated with preexisting UC. Our patients had typical symptoms of UC, and endoscopy showed pancolitis. During treatment with 5-aminosalicylic acid and steroids, severe thrombocytopenia was noted. ITP was diagnosed based on a normal to high number of megakaryocytes in the bone marrow, positive autoantibody to platelet membrane antigen, and absence of splenomegaly. Medical treatment, including increased dosage of steroids, failed to control UC and ITP in both patients. In the first patient, the platelet count recovered after colectomy, while the second patient died of a cerebral hemorrhage. We stress that a diagnosis of ITP should be considered for thrombocytopenia in patients with UC, especially those showing extensive and significant colonic inflammation, and that colectomy of UC might resolve resistant ITP.


Subject(s)
Colitis, Ulcerative/complications , Purpura, Thrombocytopenic, Idiopathic/etiology , Adult , Female , Humans , Male , Middle Aged
12.
Am J Med Sci ; 326(3): 148-51, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14501232

ABSTRACT

A 48-year-old woman was admitted because of spiking high fever, sore throat, and jaundice. A diagnosis was made of adult-onset Still disease (AOSD) presenting with acute hepatitis and very high serum ferritin levels (32,240 ng/mL), and she was treated with 2 courses of pulse therapy of methylprednisolone (2 g/day for 3 days) followed by 40 mg/day prednisolone. Subsequently, the serum level of ferritin decreased, but serum total bilirubin increased to 17.3 mg/dL. Therefore, cyclosporin was administered orally. Within the next 3 months, results of liver function tests, as well as serum levels of ferritin, soluble interleukin-2 receptor, interferon-gamma, interleukin-6, and tumor necrosis factor-alpha gradually returned to within normal limits, and cyclosporin administration was subsequently reduced gradually. The clinical presentation suggests that AOSD should be considered when liver dysfunction is accompanied with high fever and extreme hyperferritinemia, and that treatment with cyclosporin or other immunosuppressive drugs that selectively suppress cytokine production by helper T cells is a valuable option in the treatment of AOSD with very high serum ferritin levels.


Subject(s)
Antirheumatic Agents/therapeutic use , Cyclosporine/therapeutic use , Ferritins/blood , Hepatitis/complications , Hepatitis/diagnosis , Immunosuppressive Agents/therapeutic use , Still's Disease, Adult-Onset/drug therapy , Administration, Oral , Aspartate Aminotransferases/blood , Bilirubin/blood , Female , Humans , Liver/drug effects , Methylprednisolone/therapeutic use , Middle Aged
13.
Leuk Lymphoma ; 44(6): 973-6, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12854896

ABSTRACT

We describe two cases of adult T-cell leukemia/lymphoma (ATLL) with terminal ileal involvement. The first case, a 71-year-old man with lymphoma subtype of ATLL, had a polypoid lesion in the terminal ileum, in addition to a duodenal mass. The second case, a 58-year-old woman with lymphoma subtype of ATLL, had an irregular ulcerative lesion in the terminal ileum and multiple ulcers throughout the stomach. Biopsies from these lesions revealed mucosal invasion of ATLL cells in each case. In the second case, combination chemotherapy was transiently effective, resulting in the disappearance of gastric and terminal ileal lesions. Prospective and careful examination of additional cases should further characterize the clinicopathological features of terminal ileal involvement in ATLL.


Subject(s)
Ileal Diseases/pathology , Ileal Neoplasms/pathology , Leukemia-Lymphoma, Adult T-Cell/pathology , Aged , Biopsy , Fatal Outcome , Female , Humans , Intestinal Mucosa/pathology , Male , Middle Aged
14.
Med Oncol ; 20(2): 157-64, 2003.
Article in English | MEDLINE | ID: mdl-12835518

ABSTRACT

Heat shock protein (Hsp) 70 and Hsp 40 are stress proteins that cooperate as chaperones in mammalian cells. The present study was designed to determine the expression levels of Hsp 70 and Hsp 40 in colorectal cancer by immunohistochemistry and Western blot analysis. Among 50 colorectal cancer tissues studied, 80% and 14% of tumors showed specific immunoreactivity to Hsp 70 and Hsp 40, respectively. Hsp 70 and Hsp 40 were overexpressed in cancer tissue samples compared with normal tissues, on both analytic sets. However, there were no significant correlations between their expression and various clinicopathological parameters of colorectal cancer. Hsp 70 and Hsp 40 may be tumor markers for colorectal cancer.


Subject(s)
Colorectal Neoplasms/metabolism , HSP70 Heat-Shock Proteins/biosynthesis , Heat-Shock Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/biosynthesis , Blotting, Western , Female , HSP40 Heat-Shock Proteins , Humans , Immunohistochemistry , Male , Middle Aged
15.
Hepatogastroenterology ; 50(50): 422-5, 2003.
Article in English | MEDLINE | ID: mdl-12749238

ABSTRACT

BACKGROUND/AIMS: 13C-EUBT (endoscopic 13C-urea breath test), that combines the conventional urea breath test with endoscopy, provides excellent accuracy for detection of H. pylori. Recently, a simpler, less expensive and isotope-selected nondispersive infrared spectrometer has been developed for the urea breath test. We validated the diagnostic performance of 13C-EUBT using nondispersive infrared spectrometer in the management of H. pylori infection. METHODOLOGY: EUBT was performed in 232 patients by first collecting a baseline breath sample followed by upper gastrointestinal endoscopy. A 20-mL aliquot of 13C-urea solution was sprayed over the entire stomach under endoscopic guidance. Breath samples taken 0 and 20 minutes after spraying were analyzed using nondispersive infrared spectrometer. H. pylori infection was assessed by rapid urease test and histology. The cutoff level was determined by a receiver-operating characteristic curve analysis. Forty-four samples were also analyzed by the conventional isotope ratio mass spectrometer to compare results from both analyzers. We also applied the nondispersive infrared spectrometer-based EUBT to evaluate the efficacy of eradication therapy. RESULTS: Employing 2.4 per mL as the best cutoff value, the EUBT yielded an excellent diagnostic accuracy, with a sensitivity of 99% and specificity of 99%. The sensitivity and specificity of the test for assessing eradication therapy were 94% (16/17) and 100% (57/57), respectively. There was a high linear correlation between nondispersive infrared spectrometer and isotope ratio mass spectrometer (r = 0.998, p < 0.0001). CONCLUSIONS: 13C-EUBT using nondispersive infrared spectrometer is a highly accurate and rapid method for the assessment of H. pylori eradication as well as for detecting H. pylori infection. We believe that nondispersive infrared spectrometer gives more rapid and less expensive method for the management of H. pylori infection with the EUBT.


Subject(s)
Breath Tests/methods , Helicobacter pylori , Adult , Aged , Aged, 80 and over , Carbon Isotopes , Endoscopy , Female , Humans , Male , Middle Aged , ROC Curve , Spectrophotometry, Infrared , Urea
16.
Clin Biochem ; 36(3): 203-10, 2003 May.
Article in English | MEDLINE | ID: mdl-12726929

ABSTRACT

OBJECTIVES: An enzyme-linked immunosorbent assay (ELISA) using MESACUP-2 Test Mitochondria M2 kit (new-M2 ELISA) has recently become commercially available. The aim of this study was to evaluate the clinical utility of this newly developed ELISA for the diagnosis of primary biliary cirrhosis (PBC). DESIGN AND METHODS: We tested the immunoreactivity of sera from 82 Japanese PBC patients to the 2-oxo-acid dehydrogenase complex (2-OADC) enzymes by indirect immunofluorescence, enzyme inhibition assay using commercially available TRACE Enzymatic Mitochondrial Antibody (M2) Assay (EMA) kit, commercial ELISAs using MESACUP Mitochondria M2 kit (old-M2 ELISA) and new-M2 ELISA, and immunoblotting on bovine heart mitochondria. RESULTS: Each test gave the following positive results; antimitochondrial antibodies (AMA) by immunofluorescence in 71 (87%) out of the 82 sera, enzymatic inhibitory antibody to pyruvate dehydrogenase complex (PDC) by EMA in 61 (74%), immunoglobulin (Ig) G class anti-PDC antibody by old-M2 ELISA in 55 (67%), IgG/M/A class anti-E2 subunit of PDC (PDC-E2)/anti-E2 subunit of branched chain oxo-acid dehydrogenase complex (BCOADC-E2)/anti-E2 subunit of 2-oxoglutarate dehydrogenase complex (OGDC-E2) antibodies by new-M2 ELISA in 73 (89%), and IgG, IgM, or IgA class antibodies against at least one of the 2-OADC enzymes by immunoblotting in 82 (100%). Fifty-three of the 82 sera (65%) were all positive by these five assays. Of the 18 sera that were positive by new-M2 ELISA but negative by old-M2 ELISA, 12 were theoretically interpretable. Of the 11 sera that were negative for AMA by immunofluorescence but positive for at least one of anti-2-OADC enzymes by immunoblotting, four (36%) were positive by new-M2 ELISA, whereas only two and one sera were positive by EMA and old-M2 ELISA, respectively. CONCLUSIONS: Our results indicated that the sensitivity of the newly developed new-M2 ELISA was higher than that of EMA and old-M2 ELISA, and comparable with that of immunofluorescence. However, it is still unclear whether the new-M2 ELISA could replace the conventional immunofluorescence testing for routine assay requests because six (7%) sera showed discrepant results between these two assays.


Subject(s)
Enzyme-Linked Immunosorbent Assay/methods , Liver Cirrhosis, Biliary/diagnosis , Mitochondria/immunology , Adult , Aged , Aged, 80 and over , Antibodies/analysis , Antibodies/blood , Autoantibodies/blood , Dihydrolipoyllysine-Residue Acetyltransferase , Evaluation Studies as Topic , Fluorescent Antibody Technique, Indirect , Humans , Immunoblotting , Ketoglutarate Dehydrogenase Complex , Liver Cirrhosis, Biliary/blood , Middle Aged , Pyruvate Dehydrogenase Complex , ROC Curve , Reagent Kits, Diagnostic , Sensitivity and Specificity
17.
Helicobacter ; 8(2): 111-9, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12662378

ABSTRACT

BACKGROUND: In contrast to the growing amount of data concerning proton pump inhibitor-based triple therapy for Helicobacter pylori infection, it is still controversial whether proton pump inhibitor can be replaced by H2 receptor antagonist without compromising efficacy. Lafutidine is a novel potent H2 receptor antagonist with gastroprotective activities such as enhancement of gastric mucosal blood flow. METHODS: 122 outpatients with positive cultures and subsequent successful cultivation of H. pylori for antimicrobial susceptibility tests were randomized to receive a 7-day course of either lafutidine (20 mg twice daily) or lansoprazole (30 mg twice daily), plus clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Eradication was considered successful if the rapid urease test, culture, histology and [13]C-urea breath test were all negative at least 4 weeks after cessation of therapy. Cytochrome p450 2C19 genotype status using polymerase chain reaction-restriction fragment length polymorphism was also studied. RESULTS: On intention-to-treat basis, H. pylori cure was achieved in 52 of 61 (85.2%) patients and 49 of 61 (80.3%) patients for the lafutidine- and lansoprazole-based therapies, respectively. The predicted 95% confidential intervals for the 4.9% of the difference were -1.8-11.6%. Using per protocol analysis, the eradication rates were 88.2% (52/59) and 84.5% (49/58), respectively. The predicted 95% confidential intervals for the 3.7% of the difference were -2.6-10.0%. Adverse events were observed in five and six patients, from the lafutidine and lansoprazole groups, respectively, but they were generally mild. Genetic predisposition of cytochrome p450 2C19 had no significant influence on treatment outcome in both regimens. CONCLUSIONS: The lafutidine-clarithromycin-amoxicillin therapy yielded satisfactory results for eradicating H. pylori, which was comparable with those of the lansoprazole-based regimen with the same drug combination.


Subject(s)
Acetamides/administration & dosage , Anti-Ulcer Agents/administration & dosage , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Histamine H2 Antagonists/administration & dosage , Omeprazole/administration & dosage , Piperidines/administration & dosage , Pyridines/administration & dosage , 2-Pyridinylmethylsulfinylbenzimidazoles , Adult , Aged , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Aryl Hydrocarbon Hydroxylases/genetics , Clarithromycin/administration & dosage , Cytochrome P-450 CYP2C19 , Drug Resistance, Bacterial , Drug Therapy, Combination , Female , Helicobacter Infections/genetics , Humans , Lansoprazole , Male , Middle Aged , Mixed Function Oxygenases/genetics , Omeprazole/analogs & derivatives , Penicillins/administration & dosage , Prospective Studies
18.
Am J Gastroenterol ; 98(3): 551-6, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12650786

ABSTRACT

OBJECTIVE: Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. METHODS: A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1 beta by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. RESULTS: IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1 beta levels between the RE and control groups, but IL-1 beta levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. CONCLUSION: Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.


Subject(s)
Chemokines/metabolism , Esophagitis, Peptic/metabolism , Esophagus/metabolism , Adult , Aged , Aged, 80 and over , Biopsy , Chemokine CCL2/metabolism , Chemokine CCL5/metabolism , Enzyme-Linked Immunosorbent Assay , Esophagitis, Peptic/microbiology , Esophagitis, Peptic/pathology , Female , Helicobacter Infections/diagnosis , Helicobacter Infections/microbiology , Helicobacter pylori/isolation & purification , Humans , Interleukin-8/metabolism , Male , Middle Aged , Mucous Membrane/metabolism , Severity of Illness Index
19.
Eur J Gastroenterol Hepatol ; 14(10): 1093-100, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12362100

ABSTRACT

OBJECTIVE: The endoscopic (13)C-urea breath test ((13)C-EUBT), which combines the urea breath test (UBT) with endoscopy, provides high accuracy for the detection of Helicobacter pylori. This study was conducted to determine whether the (13)C-EUBT using low doses of urea and short sampling times could preserve accuracy in the management of H. pylori infection. METHODS: Three hundred and twenty-five patients were randomized to receive the EUBT with 100, 50 or 25 mg of (13)C-urea by endoscopic spraying. The breath samples collected at 5, 10 and 20 min were analysed using an isotope selected non-dispersive infrared spectrometer. H. pylori infection was assessed by the rapid urease test and histology. In each sampling schedule and protocol, cut-off values were calculated by a receiver operating characteristic curve. We applied the EUBT with 25 mg of (13)C-urea at 5 min to the assessment of eradication in 135 patients who had received the antimicrobial treatment or to the detection of the organism in 61 patients with previous partial gastrectomy. RESULTS: Based on histology and the urease test, patients who had discordant results were excluded from the analysis. Using 100 mg of urea, the sensitivity and specificity of the test were both 100% at 10 and 20 min, and the sensitivity and specificity at 5 min were best with 98.6% and 100%, respectively. With 50 mg, they were both 100% at 20 min, and the best combination of sensitivity and specificity at 5 and 10 min was 97.3-96.6% and 97.3-100%, respectively. Even with 25 mg, the sensitivity and specificity were both 100.0% at 20 min, and at the 5 min and 10 min time point, the EUBT yielded a sensitivity of 98.7% and a specificity of 100%. There was a significant positive correlation between the test values of the 5 min (13)C-EUBT with 25 mg of test urea and those of the conventional UBT. The 5 min EUBT with (13)C-urea offered high accuracy in the assessment of H. pylori eradication, with the sensitivity and specificity being 100% and 96.4%, respectively. In patients with previous gastrectomy, the EUBT provided acceptable accuracy (a sensitivity of 96.4% and a specificity of 97.0%). CONCLUSIONS: Our results indicate that the (13)C-EUBT is an accurate method for detecting H. pylori infection. The EUBT using only 25 mg of (13)C-urea at the early (5 min) time point has satisfactory diagnostic efficacy in pre- and post-eradication treatment settings, providing a less expensive and more rapid way of performing the test. The EUBT may be a reliable method of assessing H. pylori status in the remnant stomach.


Subject(s)
Breath Tests/methods , Endoscopy, Gastrointestinal/methods , Gastrointestinal Diseases/diagnosis , Helicobacter Infections/diagnosis , Helicobacter pylori , Urea/analysis , Adult , Aged , Aged, 80 and over , Carbon Radioisotopes , Humans , Middle Aged , Prospective Studies , Sensitivity and Specificity
20.
Helicobacter ; 7(5): 322-6, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12390213

ABSTRACT

A 69-year-old-woman presented with acute epigastric pain, nausea, vomiting and heartburn. Endoscopy disclosed acute gastric mucosal lesions including mucosal edema, erosions, and ulcers with blood crusts in the antrum. Touch cytology and histological assessment obtained from the affected mucosa revealed acute neutrophilic gastritis and single longer and more coiled organisms than Helicobacter pylori, suggesting Helicobacter heilmannii. Electron micropragh confirmed the characteristic morphology. Despite a positive rapid urease test, H. pylori was not isolated by culture or detected by histology and Gram smears. Based on these findings, a diagnosis of acute gastric mucosal lesions associated with H. heilmannii infection was established. This was successfully treated with a 2-week triple therapy consisting of lansoprazole, clarithromycin and metronidazole with persistent endoscopic and histological remission. This is a rare case of H. heilmannii-associated acute gastric mucosal lesions, diagnosed by morphology using touch cytology and histology. The patient might benefit from antimicrobial treatment employing the regimen effective for H. pylori.


Subject(s)
Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/diagnosis , Helicobacter Infections/complications , Helicobacter heilmannii/isolation & purification , Aged , Bacteriological Techniques , Female , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections/microbiology , Humans
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