Clinical significance of cytotoxin-associated gene A status of Helicobacter pylori among non-steroidal anti-inflammatory drug users with peptic ulcer bleeding: a multicenter case-control study

BACKGROUND: The role of Helicobacter pylori infection and especially of the cytotoxin-associated gene A (CagA) product strain in peptic ulcer bleeding among non-steroidal anti-inflammatory drugs (NSAIDs) users remains controversial. METHODS: A case-control study was carried out including 191 consecutive chronic NSAIDs users admitted to hospital because of peptic ulcer bleeding. Peptic ulcer was verified by endoscopy. Controls comprised 196 chronic NSAIDs users without signs of bleeding of similar age and gender to cases. Multivariate regression analysis was performed for further evaluation of the relationship between H. pylori, CagA status and other risk factors. RESULTS: H. pylori infection was present in 121 (63.4%) cases compared with 119 (60.7%) controls (odds ratio (OR) = 1.14, 95% CI, 0.76-1.72). CagA-positive strains were found to be significantly more frequent in cases than in controls (65/106 versus 41/99 P = 0.008). Current smoking (OR = 2.65; 95% CI, 1.14-6.15; P= 0.02), CagA status (OR = 2.28; 95% CI, 1.24-4.19; P = 0.008), dyspepsia (OR = 6.89; 95% CI, 1.84-25.76; P = 0.004) and past history of peptic ulcer disease (OR=3.15; 95% CI, 1.43-6.92; P=0.004) were associated significantly with increased risk of bleeding peptic ulcer. CONCLUSIONS: The results suggest that CagA-positive H. pylori infection is associated with a more than 2-fold increased risk of bleeding peptic ulcer among chronic NSAIDs users.     

Exercise: a potential contributing factor to the relationship between folate and dementia

OBJECTIVES: To investigate whether exercise confounds the relationship between folate and cerebrovascular events, all-cause dementia, and Alzheimer's disease. DESIGN: Prospective cohort study. SETTING: Multiple centers in Canada. PARTICIPANTS: In the Canadian Study of Health and Aging, 466 people reported exercise levels, had folate measurements, and were not demented at baseline. After 5 years, 194 had adverse cerebrovascular events, and 65 had dementia (Alzheimer's disease in 47). MEASUREMENTS: Associations between folate and cerebrovascular outcomes were examined using logistic regression in the presence and absence of exercise and other confounders. RESULTS: Folate was associated with greater risk of Alzheimer's disease (odds ratio (OR)=2.12, 95% confidence interval (CI)=1.01-4.54) and cerebrovascular outcomes (OR=2.05, 95% CI=1.11-3.78) in adjusted analyses before the inclusion of exercise and neared significance with all-cause dementia (OR=1.80, 95% CI=0.94-3.45). After the inclusion of exercise, the association between folate and dementia and Alzheimer's disease was 29% and 25% lower, respectively, and neither association was any longer significant (Alzheimer's disease: OR=1.91, 95% CI=0.89-4.11; all-cause dementia: OR=1.62, 95% CI=0.84-3.15). Exercise was a significant confounder in the relationship between folate and Alzheimer's disease (P=.03) and dementia (P=.003) but not cerebrovascular outcomes (P=.64). Unlike folate, exercise was significantly associated with Alzheimer's disease (OR=0.43, 95% CI=0.19-0.98) and dementia (OR=0.35, 95% CI=0.17-0.72) in adjusted analyses. CONCLUSION: Exercise seems to account for much of the relationship between folate and incident dementia and Alzheimer's disease.     

Folate status,genomic DNA hypomethylation,and risk of colorectal adenoma and cancer: a case control study

BACKGROUND & AIMS: Low folate intake may increase risk for colorectal cancer by inducing DNA hypomethylation. This study reports the influence of folate status, DNA methylation, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR 677C-->T and 1298A-->C), methionine synthase (MS 2756A-->G), and cystathionine-beta-synthase (CBS 844ins68) on risk for developing colorectal neoplasia. METHODS: Thirty-five patients with adenoma, 28 patients with cancer, and 76 controls were recruited for a case control study. Recruitment consent rate was 98%. Blood samples were obtained for determination of blood folates, vitamin B(12), homocysteine, DNA methylation, and genotypes. Tissue biopsy samples were obtained at colonoscopy for determination of DNA methylation in colonic mucosa. Folate status was assessed by constructing a score from estimates of dietary intake and serum and erythrocyte folate. RESULTS: Cancer patients had 26% lower folate status (95% confidence interval [CI]: 6% to 44%, P = 0.01) and 21% lower serum vitamin B(12) concentration (95% CI: -38% to 1%, P = 0.06) compared with controls. [(3)H] methyl incorporation into colonic DNA was 26% higher in patients with adenoma (95% CI: 8% to 56%, P = 0.009) and 30% higher in patients with cancer (95% CI: -3% to 48%, P = 0.08) compared with controls. High folate status was associated with decreased risk for cancer (P = 0.01 for trend). Colonic and leukocyte DNA hypomethylation were associated with increased risk for adenoma (P = 0.02 and P = 0.01 for trend, respectively) and a nonsignificantly increased risk for cancer (P = 0.09 and P = 0.08 for trend, respectively). CONCLUSIONS: Low folate status and DNA hypomethylation are associated with colorectal neoplasia.     

Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan

BACKGROUND: In Europeans and populations of European origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates. OBJECTIVE AND DESIGN: The aim of this study was to replicate in a Japanese population previously identified associations of single nucleotide polymorphisms (SNPs) within 10 candidate loci with type 2 diabetes using a relatively large sample size: 1921 subjects with type 2 diabetes and 1622 normal controls. RESULTS: A total of 15 SNPs were genotyped. Eight SNPs in five loci were found to be associated with type 2 diabetes: rs3802177 [odds ratio (OR) = 1.16 (95% confidence interval (CI) 1.05-1.27); P = 4.5 x 10(-3)] in SLC30A8; rs1111875 [OR = 1.27 (95% CI 1.14-1.40); P = 1.4 x 10(-5)] and rs7923837 [OR = 1.27 (95% CI 1.13-1.43); P = 1.0 x 10(-4)] in HHEX; rs10811661 [OR = 1.27 (95% CI 1.15-1.40); P = 1.9 x 10(-6)] in CDKN2B; rs4402960 [OR = 1.23 (95% CI 1.11-1.36); P = 8.1 x 10(-5)] and rs1470579 [OR = 1.18 (95% CI 1.07-1.31); P = 8.3 x 10(-4)] in IGF2BP2; and rs7754840 [OR = 1.28 (95% CI 1.17-1.41); P = 4.5 x 10(-7)] and rs7756992 [OR = 1.27 (95% CI 1.15-1.40); P = 9.8 x 10(-7)] in CDKAL1. The first and second strongest associations were found at variants in CDKAL1 and CDKN2B, both of which are involved in the regenerative capacity of pancreatic beta-cells. CONCLUSION: Some of these variants represent common type 2 diabetes-susceptibility genes in both Japanese and Europeans.     

Helicobacter pylori Infection with Atrophic Gastritis Is an Independent Risk Factor for Advanced Colonic Neoplasm

Background/AimsHelicobacter pylori is a major risk factor for atrophic gastritis (AG) and gastric cancer. The correlation between H. pylori, AG and colorectal neoplasm (CRN) has only been examined in a limited number of studies, and findings have been inconclusive. We aimed to investigate the association between H. pylori infection status, AG and advanced CRN.MethodsThis cross-sectional study investigated the relationship between the presence of serum anti-H. pylori IgG antibodies, AG, and advanced CRN in 6,351 consecutive asymptomatic subjects who underwent a screening colonoscopy.ResultsA total of 316 participants (5.0%) had advanced CRN. H. pylori seropositivity was 61.3%. In a univariate analysis, the presence of H. pylori infection was associated with advanced CRN (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17 to 1.91; p=0.001). H. pylori infection was associated with an increased risk of advanced CRN after adjusting for clinically relevant confounders (OR, 1.34; 95% CI, 1.04 to 1.72; p=0.023). H. pylori-related AG was significantly associated with the risk of advanced CRN (OR, 1.40; 95% CI, 1.03 to 1.91; p=0.030), whereas H. pylori infection without AG was not.ConclusionsH. pylori infection increased the risk of advanced CRN, especially when it was combined with AG. Strict colonoscopy screening and surveillance may be warranted in those with H. pylori-positive AG.     

Impact of non-steroidal anti-inflammatory drug and aspirin use on the prevalence of dyspepsia and uncomplicated peptic ulcer disease

BACKGROUND: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. METHODS: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. RESULTS: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). CONCLUSIONS: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.     

Health effects of daily indoor nitrogen dioxide exposure in people with asthma.

Household gas appliances produce nitrogen dioxide (NO2), which may be associated with an increase in symptoms in asthmatics. The relationship between indoor NO2 exposure, and respiratory symptoms in people with asthma was evaluated. Self-reported asthmatics (n=125) wore lapel badges that measured NO2 daily over 6 weeks at home. Outdoor pollutants, spores and meteorological parameters were measured daily, in addition to smoking status and demographic factors. Seven asthma symptoms were recorded in diaries, for analysis by same day and also with 1 day lag exposures, using a generalized estimating equation. Significant interactions were demonstrated between NO2 at age < or =14 yrs, with respect to the symptoms of chest tightness on the same day (odds ratio (OR): 1.29, 95% confidence interval (CI): 1.16-1.43) and with a 1 day lag (OR: 1.29, 95% CI: 1.14-1.46), breathlessness on exertion with a 1 day lag (OR: 1.13, 95% CI: 1.00-1.28), daytime asthma attacks on the same day (OR: 1.13, 95% CI: 1.02-1.26) night asthma attacks on the same day (OR: 1.16, 95% CI:1.03-1.30) and with a 1 day lag (OR: 1.15, 95% CI; 1.03-1.29) after adjustment for potential confounders. A significant interaction between NO2 and age 35-49 yrs was demonstrated for coughs with a 1 day lag (OR: 1.15, 95% CI: 1.01-1.31). Daily personal exposures to NO2 are associated with asthmatic symptoms in children.     

Esophageal Squamous Cell Carcinoma Patients Have an Increased Risk of Coexisting Colorectal Neoplasms

Background/Aims

Esophageal squamous cell carcinoma (ESCC) and colorectal neoplasms (CRNs) share risk factors. We aimed to investigate whether the CRN risk is increased in ESCC patients.

Methods

ESCC patients who underwent a colonoscopy within 1 year of diagnosis were retrospectively analyzed. Patients were matched 1:3 by age, gender, and body mass index to asymptomatic controls. CRN was defined as the histological confirmation of adenoma or adenocarcinoma. Advanced CRN was defined as any of the following: ≥3 adenomas, high-grade dysplasia, villous features, tumor ≥1 cm, or adenocarcinoma. The risk factors for both CRN and advanced CRN were evaluated by univariate and multivariate analyses.

Results

Sixty ESCC patients were compared with 180 controls. The ESCC group had significantly higher numbers of CRNs (odds ratio [OR], 2.311; 95% confidence interval [CI], 1.265 to 4.220; p=0.006) and advanced CRNs (OR, 2.317; 95% CI, 1.185 to 4.530; p=0.013). Significant risk factors for both CRN and advanced CRN by multivariate analysis included ESCC (OR, 2.157, 95% CI, 1.106 to 4.070, p=0.024; and OR, 2.157, 95% CI, 1.045 to 4.454, p=0.038, respectively) and older age (OR, 1.068, 95% CI, 1.032 to 1.106, p<0.001; and OR, 1.065, 95% CI, 1.024 to 1.109, p=0.002, respectively).

Conclusions

The rates of CRN and advanced CRN are significantly increased in ESCC. Colonos-copy should be considered at ESCC diagnosis.     

血浆高半胱氨酸水平与动脉粥样硬化性类烟雾病的相关性

目的 探讨血浆高半胱氨酸(homocysteine,Hcy)水平与动脉粥样硬化性类烟雾病的关系.方法 选取动脉粥样硬化性类烟雾病缺血性卒中患者(类烟雾病组)95例、大动脉粥样硬化性卒中患者(卒中组)95例、健康志愿者(对照组)94例.检测血浆Hcy水平,收集人口统计学资料、血管危险因素和实验室检查结果 .分析血浆Hcy水平与动脉粥样硬化性类烟雾病的相关性.结果 类烟雾病组高血压、高脂血症、既往卒中或短暂性脑缺血发作(transient ischemic attack,TIA)史、高同种半胱氨酸血症(hyperhomocysteinemia,HHcy)的患者构成比以及收缩压、总胆固醇、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、Hcy、维生素B12、叶酸水平与对照组比较差异有统计学意义(P均<0.017);类烟雾病组既往卒中或TIA史的患者构成比以及收缩压和叶酸水平与卒中组比较差异有统计学意义(P均<0.017).与对照组比较,多变量logistic回归分析显示,HHcy[优势比(odds ratio,OR)1.806,95%可信区间(confidence interval,CI)1.348~2.420;P<0.001]、 既往卒中或TIA史(OR 3.519,95%CI 1.709~7.028;P=0.013)、收缩压(OR 1.099,95%CI 1.035~1.168;P=0.002)、LDL-C(OR 38.473,95%CI 6.384~231.842;P<0.001)是动脉粥样硬化性类烟雾病的独立危险因素,HDL-C(OR 0.025,95%CI 0.001~0.768;P=0.035)和叶酸(OR 0.779,95%CI 0.608~0.996;P=0.047)是其独立保护因素;与卒中组比较,多变量logistic回归分析显示,既往卒中或TIA史(OR 3.280,95%CI 1.664~6.466;P=0.001)、收缩压(OR 1.019,95%CI 1.002~1.035;P=0.029)是类烟雾病的独立危险因素,叶酸(OR 0.845,95%CI 0.750~0.952;P=0.006)是其独立保护因素.结论 血浆Hcy水平升高是动脉粥样硬化性类烟雾病的独立危险因素,在其发病机制中起重要作用.     

Loss of genomic imprinting of insulin-like growth factor 2 is strongly associated with cellular proliferation in normal hematopoietic cells

OBJECTIVE: The human insulin-like growth factor 2 (IGF2) gene was thought to be imprinted and expressed only from the paternal allele in normal tissue. MATERIALS AND METHODS: Initially, we analyzed the imprinting status of IGF2 in bone marrow cells from 49 patients with myelodysplastic syndromes (MDS) utilizing the Apa I polymorphism of IGF2. Thirteen bone marrow and 14 peripheral blood samples from normal individuals served as controls. We utilized normal peripheral blood T lymphocytes to examine the relationship between genomic imprinting and cell proliferation. Expression of IGF2 was quantified by real-time PCR and proliferation of T cells was measured by 3H-thymidine incorporation. Furthermore, methylation status of the imprinting controlling region (ICR) was analyzed by subcloning and sequencing of genomic DNA after sodium bisulfite modification. RESULTS: Among 24 patients who were heterozygous for IGF2, loss of imprinting (LOI) occurred in 22 cases (92%). Surprisingly, LOI of IGF2 occurred in the normal bone marrow cells, but the normal peripheral blood cells showed retention of imprinting (ROI). Unstimulated normal T cells showed ROI. After 24 hours of exposure to PHA, these cells changed their IGF2 imprinting status from ROI to LOI. Concomitantly, their IGF2 RNA levels increased up to sixfold and their proliferation increased 10- to 20-fold. In contrast, normal T cells not stimulated with PHA did not develop LOI of IGF2, had negligible levels of IGF2 RNA, and did not increase their proliferation. In unstimulated T cells, the CpG islands of the ICR were completely methylated on one allele and nearly completely unmethylated on the other allele. After PHA stimulation, the CpG islands at the ICR became completely methylated on both alleles. CONCLUSION: LOI of IGF2 is strongly associated with cell proliferation and is not limited to cancer cells.     

Metabolic syndrome is an independent risk factor for synchronous colorectal neoplasm in patients with gastric neoplasm

Background and Aim: There are no data on how metabolic syndrome (MetS) affects the prevalence of synchronous colorectal neoplasm (CRN) in gastric neoplasm (GN) patients. The aim of this study was to investigate a model for risk stratification for colorectal screening by evaluating the clinical characteristics of synchronous CRN in GN patients classified according to the presence of MetS. Methods: A cross‐sectional, case‐control study of 492 patients (368 males and 124 females) with GN, and 492 age‐matched healthy controls undergoing simultaneous upper endoscopy and colonoscopy, was conducted. Results: The GN group involved 446 patients without MetS, and 46 patients with MetS. In total, 177 (39.7%) and 28 (60.9%) synchronous CRN were detected in GN patients without MetS and with MetS, respectively (P = 0.006). A total of 143 (34.7%) synchronous colorectal adenomas were detected in GN patients without MetS, whereas 17 (48.6%) were detected in GN patients with MetS (P = 0.101), as well as more synchronous colorectal cancers (11.2% vs 37.9%, P < 0.001). A multivariate logistic regression analysis revealed that the presence of GN (OR = 1.54, 95% CI: 1.18–2.00, P = 0.001) and the presence of MetS (odds ratio = 1.82, 95% confidence interval: 1.19–2.78, P = 0.006) were significant independent risk factors associated with the prevalence of CRN. The frequency of synchronous CRN in GN patients with MetS was 1.96 times greater than that in the GN group without MetS. Conclusion: The risk of synchronous CRN is significantly increased by the presence of GN, especially in MetS patients. Screening for synchronous CRN is highly recommended for GN patients with MetS.     

Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States

BACKGROUND & AIMS: Oxidative stress is thought to play a role in liver injury. Hepatic iron may promote liver injury, whereas antioxidant vitamins and minerals may inhibit it, but few clinical studies have examined such relationships. We analyzed the associations of serum iron measures and antioxidant concentrations with abnormal serum alanine transaminase (ALT) activity in a large, national, population-based study. METHODS: A total of 13,605 adult participants in the third U.S. National Health and Nutrition Examination Survey (NHANES III), 1988-1994, underwent phlebotomy. Exclusions included excessive alcohol consumption, hepatitis B and C, and iron overload. RESULTS: Elevated ALT levels were found in 3.1% of the population. In univariate analysis, factors associated with abnormal ALT levels (P < 0.05) included higher transferrin saturation and iron and selenium concentrations, and lower vitamin C, alpha and beta carotene, and lutein/zeaxanthin concentrations. In multivariate logistic regression analyses, elevated ALT level was associated positively with increasing deciles of transferrin saturation (odds ratio [OR] per decile, 1.10; 95% confidence interval [CI], 1.03-1.18) and iron concentration (OR, 1.13; 95% CI, 1.06-1.21). Abnormal ALT level was associated negatively with increasing deciles of alpha carotene (OR, 0.82; 95% CI, 0.72-0.94), beta carotene (OR, 0.91; 95% CI, 0.86-0.96), beta cryptoxanthin (OR, 0.91; 95% CI, 0.84-0.99), lutein/zeaxanthin (OR, 0.90; 95% CI, 0.84-0.96), and a variable combining the 5 carotenoid measures (OR, 0.89; 95% CI, 0.83-0.95). Vitamin C was associated inversely, but only at the highest concentrations. CONCLUSIONS: In this large, national, population-based study, the risk for apparent liver injury was associated with increased iron and decreased antioxidants, particularly carotenoids.     

Steatosis is a cofactor in liver injury in hemochromatosis

BACKGROUND & AIMS: Obesity-related steatosis is an increasingly common histologic finding and often coexists with other chronic liver diseases. Although obesity and steatosis are recognized risk factors for more advanced fibrosis in chronic hepatitis C and alcoholic liver disease, it has not been determined whether these factors influence the progression of other diseases in which steatosis is not a feature of the primary liver insult. METHODS: We studied 214 patients with hemochromatosis who were homozygous for the C282Y substitution in HFE and had undergone liver biopsy prior to phlebotomy. RESULTS: Steatosis was present in 41.1% of these patients, and 14.5% had moderate or severe steatosis. Median serum alanine aminotransferase (ALT) and ferritin levels were higher (P < .001), and median transferrin saturation (P = .01) and hepatic iron concentration (HIC) were lower (P = .003) in subjects with steatosis compared with subjects without steatosis. Bivariate analysis revealed a significant association between steatosis and fibrosis (P = .001). Following multiple logistic regression, steatosis was independently associated with fibrosis (odds ratio [OR] 4.3, 95% confidence interval [CI]: 2.1-8.8; P < .001) along with male sex (OR, 5.1; 95% CI: 2.0-12.5; P < .001), excess alcohol consumption (males > or = 50 g/day, females > or = 40 g/day) (OR, 3.9; 95% CI: 1.8-8.5; P = .001), and hepatic iron content (OR, 1.4; 95% CI: 1.2-1.6; P < .001). Both higher BMI (OR, 3.3; 95% CI: 1.8-6.3; P < .001) and alcohol consumption (males > or = 30 g/day, females > or = 10 g/day) (OR, 3.4; 95% CI: 1.2-10.0; P = .023) were independently associated with the presence of steatosis. CONCLUSIONS: These findings indicate that obesity-related steatosis may have a role as a cofactor in liver injury in hemochromatosis. This has important clinical implications and suggests that obesity should be actively addressed in the management of patients with hemochromatosis, as well as other liver diseases.     

Predictors of switching from nonsteroidal anti-inflammatory drugs to corticosteroids in patients with acute pericarditis and impact on clinical outcome

BackgroundAspirin and nonsteroidal anti-inflammatory drugs (A/NSAIDs) are the mainstay treatments for acute pericarditis. We sought to identify factors predicting failure of A/NSAIDs and switch to corticosteroid treatment (STCT) as well as the impact of STCT on pericarditis recurrence.MethodsWe enrolled 148 patients with acute pericarditis receiving A/NSAIDs (n=110) or corticosteroids (n=38) as first-line treatment according to clinical indications. In case of poor response to A/NSAIDs (n=37), STCT was performed and factors contributing to such failure were explored. All patients were followed-up prospectively for 18 months for pericarditis recurrence.ResultsIn multivariate analysis, female sex (odds ratio [OR] =3.57, 95% confidence interval [CI]: 1.00-12.5), age (per decade, OR=0.75, 95% CI: 0.57-0.99), PR-segment depression (OR=4.43, 95% CI: 1.02-19.34), and a secondary cause of pericarditis (OR=13.52, 95% CI: 1.51-117.8) were independent predictors of poor response to A/NSAIDs and STCT. In cox regression analysis, the risk of recurrence was higher in patients requiring STCT (hazards ratio [HR] =3.22, 95% CI: 1.70-6.13) and in those initially treated with corticosteroids (H=2.06, 95% CI: 1.01-4.21) than in patients receiving A/NSAIDs only.ConclusionsTreatment failure with A/NSAIDs in acute pericarditis can be anticipated by certain patient characteristics. STCT identifies patients who are at the highest risk for recurrences, a risk that is approximately threefold higher than that of A/NSAIDs and 1.5-fold higher than that of corticosteroids as first-line treatment.     

Impact of Non-steroidal Anti-inflammatory Drug and Aspirin Use on the Prevalence of Dyspepsia and Uncomplicated Peptic Ulcer Disease

Background: Non-steroidal anti-inflammatory drug and aspirin (here collectively called NSAIDs) use is the second most common aetiologic factor for peptic ulcer disease and a major factor for peptic ulcer complications. The role of NSAIDs in the pathogenesis of uncomplicated peptic ulcer is less well understood and the interaction between NSAIDs and Helicobacter pylori infection on ulcer development is controversial. The aim of the present study was to examine the role of NSAIDs in the occurrence and clinical features of uncomplicated peptic ulcer disease. Methods: A total of 1091 consecutive patients referred for open-access upper gastrointestinal endoscopy by general practitioners (GPs) were enrolled. The use of NSAIDs was gathered from a structured questionnaire completed by the patients and from patient files by GPs. The exclusion criteria were previous H. pylori eradication and gastric surgery, as well as symptoms and/or signs suggestive of acute gastrointestinal bleeding. Results: Of the whole study group (n = 1091), 76 (7%) patients had a peptic ulcer. Thirty patients had an NSAID-use-associated peptic ulcer and 46 patients a non-NSAID-use peptic ulcer. Of patients with chronic gastritis (n = 599), 71% were H. pylori-positive and 108 used NSAIDs. Of those with chronic gastritis, 23 had an NSAID-use-associated peptic ulcer and 38 a non-NSAID ulcer. Of patients with normal gastric histology (n = 492), 75 patients used NSAIDs, 7 had an NSAID ulcer and 8 a non-NSAID ulcer. The only independent risk factor for peptic ulcer in patients using NSAIDs was H. pylori infection (odds ratio (OR) 3.1, 95% confidence interval (CI) 1.3-7.3), whereas dyspepsia (OR 1.0, 95% CI 0.4-2.4), male sex (OR 1.4, 95% CI 0.6-3.4), age (OR 1.0 per decade, 95% CI 0.8-1.3) and anaemia (OR 2.9, 95% CI 0.9-8.7) were not risk factors. In patients not using NSAIDs, independent risk factors for peptic ulcer were dyspepsia (OR 4.3, 95% CI 2.1-8.8), male sex (OR 2.0, 95% CI 1.1-2.8), age (OR 1.2 per decade, 95% CI 1.0-1.5), anaemia (OR 6.2, 95% CI 2.6-14.9) and H. pylori infection (OR 7.5, 95% CI 3.4-16.6). When comparing patients using NSAIDs or not, the OR of patients on NSAIDs for peptic ulcer was 2.7 (95% CI 1.5-5.0) among patients with chronic H. pylori gastritis (n = 424) and 5.3 (95% CI 1.8-15.0) among patients with normal gastric mucosa (n = 492). Conclusions: The use of NSAIDs increases the risk of peptic ulcer 3- and 5-fold in H. pylori-positive and H. pylori-negative patients, respectively. Dyspepsia is a poor predictor of peptic ulcer among patients using NSAIDs, and serologic H. pylori testing and treatment for chronic NSAID users is recommended.     

Irritable bowel syndrome and surgery: a multivariable analysis

BACKGROUND & AIMS: Patients with irritable bowel syndrome (IBS) have high surgical rates. We investigated the demographic and medical factors independently associated with surgical histories of health examinees. METHODS: We applied multiple stepwise logistic regression analysis to self-completed questionnaire data from 89,008 examinees, assessing 6 surgeries as outcomes. We assessed questionnaire/physician record agreement of physician-diagnosed IBS and surgical history on 201 randomly selected examinees with > or =3 years of records. RESULTS: Questionnaire/record agreement for IBS and surgery was 83.6% (kappa = 0.68) and 95.5%-100.0% (kappa = 0.82-1), respectively. IBS was reported by 4587 examinees (5.2%) (1382 men [3.0%] and 3205 women [7.5%]). Subjects with and without IBS, respectively, reported the following surgical procedures: cholecystectomy, 569 (12.4%) versus 3428 (4.1%), P < 0.0001; appendectomy, 967 (21.1%) versus 9906 (11.7%), P < 0.0001; hysterectomy, 1063 (33.2%) versus 6751 (17.0%), P < 0.0001; back surgery, 201 (4.4%) versus 2436 (2.9%), P < 0.0001; coronary artery surgery, 127 (2.8%) versus 2033 (2.4%), P > 0.05; peptic ulcer surgery, 22 (0.5%) versus 277 (0.3%), P > 0.05. Among independent surgery associations, IBS was associated with cholecystectomy (adjusted odds ratio [OR], 2.09; 95% confidence interval [CI], 1.89-2.31; P < 0.0001), appendectomy (OR, 1.45; 95% CI, 1.33-1.56; P < 0.0001), hysterectomy (OR, 1.70; 95% CI, 1.55-1.87; P < 0.0001), and back surgery (OR, 1.22; 95% CI, 1.05-1.43; P = 0.0084). CONCLUSIONS: Health examinees with physician-diagnosed IBS report rates of cholecystectomy 3-fold higher, appendectomy and hysterectomy 2-fold higher, and back surgery 50% higher than examinees without IBS; IBS is independently associated with these surgical procedures.     

Incidence,Predictors and Outcomes of Contrast Induced Nephropathy in Patients with ST Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Background:Contrast induced nephropathy (CIN) is considered one of the most common causes of hospital acquired renal failure and severely affects morbidity and mortality. Our objective was to investigate incidence, predictors and outcomes of CIN in patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI).Methods:The study was conducted on 550 patients with STEMI subjected to PPCI. Patients were classified into two groups according to the occurrence of CIN; group I (Patients without CIN) and group II (Patients with CIN). The two groups were assessed for the clinical outcomes including mortality and major adverse cardiac events (MACE).Results:Incidence of CIN was 10.6%, multivariate regression analysis identified the independent predictors of CIN including; age > 60 years OR 6.083 (CI95% 3.143–11.77, P = 0.001), presence of diabetes mellitus OR 2.491 (CI95% 1.327–4.675, P = 0.005), non-steroidal anti-inflammatory drugs (NSAIDs) use OR 2.708 (CI95% 1.393–5.263, P = 0.003), the volume of contrast agent >200 ml OR 6.543 (CI95% 3.382–12.65, P = 0.001) and cardiogenic shock OR 4.514 (CI95% 1.738–11.72, P = 0.002). Mortality was higher in group II than group I (11.9% vs. 4.4% respectively, P = 0.015). The incidence of MACE were higher in group II than group I (heart failure; 18.6% vs. 7.3%, cardiac arrest; 8.5% vs. 2.8% and cardiogenic shock; 16.9% vs. 6.9% with P. value = 0.003, 0.024, 0.007 respectively).Conclusion:Contrast induced nephropathy was associated with increased morbidity and mortality. The independent predictors of CIN were advanced age, diabetes mellitus, NSAIDs use, the volume of contrast agent >200 ml and cardiogenic shock.     

Determinants of impaired renal function with use of nonsteroidal anti-inflammatory drugs: the importance of half-life and other medications.

PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with renal function, but little is known about the effects of the half-life of these agents, or the use of other medications, on renal function. SUBJECTS AND METHODS: Medication use was assessed during a standardized interview in a cross-sectional study of 802 patients undergoing total joint replacement because of osteoarthritis. Preoperative blood samples were used to estimate creatinine clearance using a standard formula that takes age, sex, and weight into account. Impaired renal function was defined as an estimated creatinine clearance less than 60 mL/min (fifteenth percentile). Multivariable logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between NSAID use (alone or in combination with diuretics or angiotensin-converting enzyme [ACE] inhibitors) and impaired renal function. RESULTS: NSAID use per se was only marginally associated with impaired renal function (OR = 1.4; 95% CI, 0.9 to 2.2). This association was almost exclusively the result of the use of NSAIDs with a half-life of 4 or more hours (OR = 2.6; 95% CI: 1.2 to 5.7). Patients who used diuretics with NSAIDs (OR = 3.7; 95% CI: 1.7 to 8.3) or without NSAIDs (OR = 3.5; 95% CI: 1.6 to 7.6) had a higher risk of impaired renal function than did patients using NSAIDs alone (OR = 1.6) or none of these drugs (reference). A similar but less pronounced pattern was observed for ACE inhibitors. CONSLUSION: NSAID-associated impaired renal function seems to be mainly the result of compounds with intermediate-long half-life. We found no evidence that the adverse effects of diuretics and ACE inhibitors on renal function were greater in those who also used NSAIDs.     

山东地区农民反流性食管炎相关危险因素的研究

目的 进行农民反流性食管炎（RE）发病相关危险因素的调查。方法 2006年5月对山东烟台牟平区高陵镇常住农民进行胃镜及病理组织学检查及症状危险因素调查。结果 共调查556例,男性269例,女性287例。年龄34～90（60．7±8．15）岁。内镜发现糜烂性RE101例（18．2％）;其中洛杉矶分级A级37例,B级57例,C级3例,D级4例。RE在男性中比例更高（P〈0．001）;患者年龄（P=0．041）、务农时间（P=0．040）、Z线距离门齿的长度（P=0．001）与发病有相关性。吸烟（OR 1．894,95％CI 1．207～2．974）、饮浓茶（OR 2．900,95％CI 1．651～5．092）、使用非甾体类抗炎药（NSAIDs）（OR 2．159,95％CI 1．166～3．997）、贲门松弛（OR 13．630,95％CI 7．370～25．190）是发病危险因素。而身高、体重、腹围、体重指数、饮酒、特殊饮食习惯、糖尿病、腹部手术史等与之无关（P〉0．05）。RE组合并消化性溃疡的患者12例,高于非RE组;RE组合并胃体萎缩的患者14例,少于非RE组,但均未达到统计学意义。本组总调查人群幽门螺杆菌（Hp）感染率为51．3％（273／556）,RE组为37．1％（36／97）,非RE组为54．5％（237／435）（P=0．002）（OR0．492,95％C10．313～0．776）。多因素分析显示,男性、Z线距门齿长度短、贲门松弛、服用NSAIDs是RE发病的危险因素,而Hp感染可减少RE的发病。结论 男性、高龄、Z线距门齿长度短、贲门松弛、无Hp感染等因素与RE的发病有相关性,吸烟、饮浓茶、服用NSAIDs、务农时间长是发病的危险因素。     

Nutrient patterns and risk of esophageal squamous cell carcinoma: a case-control study

Although Iran is a high-risk country for esophageal squamous cell carcinoma (ESCC), the contribution of overall nutrient intakes to this high incidence rate is not yet clear. The aim of this study was to examine the association between nutrient patterns and risk of ESCC in Iran. Forty-seven patients with ESCC and 96 frequency-matched hospital controls underwent private interviews, and dietary habits were collected using a validated food-frequency questionnaire. Factor analysis was conducted and two major nutrient patterns were retained; factor 1 (high in pantothenic acid, vitamin C, potassium, vitamin B(6), magnesium, folate, thiamin, copper, carbohydrate, vitamin K, niacin, α-tocopherol, zinc, total fiber, fluoride, and polyunsaturated fatty acids) and factor 2 (high in saturated fatty acid, biotin, selenium, monounsaturated fatty acids, riboflavin, sodium, fat, cholesterol, calcium, phosphorus, protein, iron, vitamin E, manganese, vitamin D, and vitamin B(12)). Factor 2 was inversely associated with ESCC (OR = 0.06, 95% CI: 0.01-0.28; P = 0.008), whereas no significant association was found for factor 1 (OR = 0.45, 95% CI: 0.11-1.82). The results of the present study suggested a possible role for a nutrient pattern similar to factor 2 in reducing the risk of ESCC.