Hemodialysis-induced P-wave signal-averaged electrocardiogram alterations are indicative of vulnerability to atrial arrhythmias.

BACKGROUND: Atrial fibrillation (AF) is the most common supraventricular arrhythmia, often occurring during hemodialysis (HD). Prolongation of the total filtered P-wave duration (PWD) and reduction of the root mean square voltages for the last 20 ms of the P wave (RMS20) on a P-wave signal-averaged electrocardiogram (P-SAECG) are predictors of AF. We investigated whether HD induces alterations of P-SAECG, and determined the influential factors. METHODS AND RESULTS: Thirty-three end-stage kidney disease patients (66.7 ± 12.6 years, 23 males) undergoing maintenance HD were enrolled in this study. Digital ambulatory P-SAECG monitoring and laboratory examination of serum proteins and ions were carried out before, during, and after the HD sessions. Data were analyzed by multiple regression analysis. PWD was significantly prolonged, and RMS20 significantly reduced, during HD. These values recovered after completion of HD. Multiple regression analysis showed that prolongation of PWD significantly correlated with HD duration and the rate of removal of body fluid. On the other hand, RMS20 significantly correlated with HD duration and blood urea nitrogen variation. CONCLUSIONS: HD resulted in prolongation of PWD and reduction of RMS20, indicating the vulnerability of HD patients to AF. These P-SAECG changes correlated with HD duration and the rate of removal of the body fluid. These findings underline the importance of the control of dialysis variables in the prevention of atrial arrhythmias following HD.

Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of colorectal cancer: a hospital-based case-control study in Japan.

OBJECTIVE: Although associations between dietary HCA intake and colorectal cancer risk have been investigated, results have been suggestive but inconsistent. The aim of this hospital-based case-control study was to examine the impact of heterocyclic amine (HCA) intake on colorectal cancer risk. A further objective was to investigate the possible effect of genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on colorectal cancer. MATERIAL AND METHODS: HCA exposure data were assessed using a self-administered food frequency questionnaire, and estimated HCA intake was verified by measuring the PhIP value in human hair. A total of 117 cases and 238 controls were included in these analyses. Odds ratios (ORs) were calculated using conditional logistic regression analysis to compare intake levels between the first and third tertiles. RESULTS: No statistically significant increase in the risk of colorectal cancer with respect to total HCA intake was shown by analysis (OR = 0.99, 95% CI = 0.21-4.81). Furthermore, no association with risk was seen for individual HCAs, including PhIP, MeIQ, and MeIQx. Although variant alleles of CYP1A2 were associated with colorectal cancer (OR = 0.27; 95% CI = 0.07-0.99), genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not influence the association of HCA intake with colorectal cancer. CONCLUSIONS: In the present study in subjects with low HCA exposure and with a limited sample size, no association was found between HCA intake and colorectal cancer, or any evidence of influence by genetic polymorphisms of NAT2, CYP1A1, and CYP1A2.

Association between dietary heterocyclic amine levels, genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 and risk of stomach cancer: a hospital-based case-control study in Japan.

BACKGROUND: Although the associations between grilled (broiled) or barbecued meats or fish intake and stomach cancer risk have been investigated, the evidence implicating heterocyclic amine (HCA) intake as a cause of stomach cancer is limited. We conducted a case-control study to investigate the association between HCA intake and stomach cancer risk. We also investigated the possible effect of genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on stomach cancer. METHODS: HCA exposure data were assessed using a self-administered food-frequency questionnaire, and estimated HCA intake was verified by measuring 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) values in human hair. A total of 149 cases and 296 controls were included in the analyses. Odds ratios (ORs) were calculated, using conditional logistic regression analysis, to compare intake levels between the first and third tertiles. RESULTS: Results showed no statistically significant increase in the risk of stomach cancer with respect to total HCA intake (OR, 1.11; 95% confidence interval [CI], 0.36, 3.49), or with respect to the intake of individual HCAs; namely, PhIP, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ), and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). Genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 did not influence the association of HCA intake with stomach cancer. CONCLUSION: In the present study, with a limited sample size of subjects with low HCA exposure, no association was found between HCA intake and stomach cancer, nor was there any evidence of any influence by genetic polymorphisms of NAT2, CYP1A1, and CYP1A2 on the risk of stomach cancer.

Screening of 214 single nucleotide polymorphisms in 44 candidate cancer susceptibility genes: a case-control study on gastric and colorectal cancers in the Japanese population.

OBJECTIVES: Single nucleotide polymorphisms (SNPs) have potential as markers for identifying genes responsible for common diseases and for personalized medicine. To investigate the association between polymorphisms and gastrointestinal (gastric and colorectal) cancer, we performed a hospital-based case-control study in Japan. METHODS: We screened a total of 214 SNPs in 44 candidate genes by using a mass spectrometry-based technique (MassARRAY; Sequenom, Inc., San Diego, CA). In this study, 153 patients and 302 controls for gastric cancer and 121 patients and 245 controls for colorectal cancer were matched with regard to age, sex, and residential area. Genes were selected based on their possible interactions with the environment and lifestyle, and the candidate genes constitute those encoding xenobiotic metabolism enzymes, DNA repair enzymes, and other stress-related proteins. Each polymorphism was tested in controls to ensure its fit with Hardy-Weinberg equilibrium. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by conditional logistic regression analysis to estimate the association between genetic polymorphisms and the risk of gastric and colorectal cancers. RESULTS: Twenty-one SNPs in nine genes were associated with the risk of gastric cancer (P < 0.05) and 15 SNPs in nine genes were associated with the risk of colorectal cancer (P < 0.05). CONCLUSIONS: The findings of the present study will be the basis for future large-scale association studies of gene-environment factors using the candidate gene approach for the Japanese population.

Epidemiological and clinical study of sporadic acute hepatitis E caused by indigenous strains of hepatitis E virus in Japan compared with acute hepatitis A.

BACKGROUND: We compared acute hepatitis E (AH-E) and acute hepatitis A (AH-A) to investigate the epidemiology, clinical features, and prognosis of AH-E caused by an indigenous hepatitis E virus (HEV) in Japan. METHODS: We enrolled 58 patients diagnosed with AH-A or AH-E (32 men and 26 women; age, 20-72 years) from December 1997 to October 2002. Phylogenetic analysis of the partial 412-nucleotide sequence of open reading frame (ORF) 2 was performed in patients with AH-E. RESULTS: Regarding the geographic distribution of the HEV genotype, genotype III was principally distributed in Honshu Island, and genotype IV in Hokkaido Island ( P = 0.0034). The phylogenetic analysis of the ORF2 region revealed that there were significant geographic differences in the distribution of the HEV strains in Japan, with some strains being widespread and some, localized. In comparison with AH-A patients, those with AH-E were older (56.1 +/- 10.6 vs 45.9 +/- 10.8 years; P = 0.0017). The proportion of males among patients with AH-E was significantly higher ( P = 0.0001). Pyrexia was often observed in AH-A, and malaise in AH-E. Laboratory data indicate that AH-E induces a weak immunological reaction, whereas jaundice appears earlier in AH-E than in AH-A. One patient with AH-E died of acute hepatic failure, but none of those with AH-A died during the study period. CONCLUSIONS: Our results suggest that there are geographical differences between HEV strains in Japan, and that AH-E is more common in males and older patients than AH-A. Laboratory data indicate a weak immunological reaction and early appearance of jaundice in AH-E.

Atrophic gastritis, Helicobacter pylori, and colorectal cancer risk: a case-control study.

BACKGROUND: Helicobacter pylori is a major risk factor for atrophic gastritis and gastric cancer. Various extragastric manifestations of H. pylori infection have also recently been suggested. However, the correlation between H. pylori and colorectal cancer (CRC) is controversial. The aim of this study was to examine the correlation between H. pylori, serum gastrin level, and atrophic gastritis with CRC. MATERIALS AND METHODS: Subjects were patients with CRC; controls were participants of a health check-up program that was conducted between October 1998 and March 2002 at four hospitals in Nagano Prefecture. For 121 newly diagnosed CRC cases, two controls matched by age (within 3 years), gender, and residence were randomly selected from the program participants. We conducted questionnaires and obtained blood samples from the cases and their controls. Consequently, the CRC cancer pairs consisted of 113 cases and 226 controls. RESULTS: Neither H. pylori infection nor gastrin level nor atrophic gastritis showed any association with a risk for CRC. However, serologically determined atrophic gastritis demonstrated significant elevation in odds ratios (ORs) for rectal cancer (OR = 3.15, 95% confidence interval; 1.19-8.35). CONCLUSIONS: Gastric conditions such as chronic H. pylori infection and atrophic gastritis are unlikely to increase the risk for CRC, although atrophic gastritis may increase the risk of rectal cancer.

Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa.

High serum level of GH in the presence of low plasma level of insulin-like growth factor-I (IGF-I) is one of the endocrinological features of anorexia nervosa (AN). Whether the amount of endogenous GH is not enough to increase IGF-I is not certain. We studied the effect of recombinant human growth hormone (rhGH) on the GH-IGF-I axis and on malnutrition-related disorders in this syndrome. Twenty patients with AN were divided into two groups; one (N = 13) was given rhGH (0.33 mg/day), and the other (N = 7) was given placebo for 6 or 12 months, respectively. During each treatment, levels of serum GH, plasma IGF-I, serum thyroid hormones, serum cholesterol, fasting plasma glucose and cardiac function were monitored. Changes in body mass index (BMI) and calorie taken were also evaluated. Plasma IGF-I level increased from 74.4 +/- 41.9 to 269.0 +/- 31.2 microg/L (P<0.001) during administration of rhGH, which associated with a decrease in serum GH level from 17.0 +/- 15.0 to 1.6 +/- 0.8 microg/L (P<0.001). Administration of rhGH increased BMI, body temperature, fasting plasma glucose level, and food intake. Serum level of triiodothyronine, but not thyroxine, increased during treatment with rhGH. The treatment decreased serum levels of both total and HDL-cholesterol. Studies with echocardiography showed an increase in cardiac output during the treatment with rhGH. These improvements were not observed in patients treated with placebo. Administration of rhGH is recommended as one of the methods of managing the patients with AN.

Folate, vitamin B6, vitamin B12, and vitamin B2 intake, genetic polymorphisms of related enzymes, and risk of colorectal cancer in a hospital-based case-control study in Japan.

We conducted a case-control study to investigate the association of nutrient intake involved in the one-carbon pathway of folate for DNA methylation and DNA synthesis and the related enzyme genetic polymorphisms with colorectal cancer. Cases were 107 patients newly diagnosed with colorectal cancer. Controls were 224 subjects matched with cases by sex, age, and residential area. Nutrient intake was assessed by a self-administered, semiquantitative food-frequency questionnaire. Four genetic polymorphisms-MTHFR C677T and A1298C, MTRR A66G, and ALDH2 Glu487Lys-were determined using blood samples. Odds ratios were calculated using conditional logistic regression analysis adjusted for smoking, alcohol consumption, body mass index, and dietary fiber intake. Although folate intake was inversely associated with colorectal cancer, this association was attenuated after further controlling for dietary fiber intake. Neither vitamin B6, vitamin B12, nor vitamin B2, nor any genetic polymorphism was significantly associated with colorectal cancer. MTRR polymorphism interacted with the association of folate (P for interaction = 0.04) or vitamin (P for interaction = 0.02) with colorectal cancer, although the other polymorphisms did not interact with any nutrient intake. In conclusion, the study did not support the existing hypothesis of gene-nutrient interaction in colorectal carcinogenesis.

Fulminant diabetes mellitus associated with pregnancy: case reports and literature review.

We report two cases of type 1 diabetes mellitus fulminantly developed as diabetic ketoacidosis (DKA) at 19 weeks of gestation and immediately after delivery. Development of type 1 diabetes around pregnancy is not rare, but its fulminant development is highly uncommon. We also review the relevant literature concerning mostly Japanese cases. In our cases, the group of patients with fulminant progressive diabetes mellitus associated with pregnancy required insulin replacement therapy even after the acute period and showed high value of pancreatic exocrine enzymes, i.e. amylase, elastase, and lipase. The phenotype of this group was similar to "nonautoimmune, fulminant type 1 diabetes" described by Imagawa et al., where the laboratory data of type 1 diabetes-related autoantibodies showed negative. It is well known that autoimmune diseases are in good control during pregnancy. Our present finding suggests that this type of fulminant type 1 diabetes mellitus associated with pregnancy might develop as a consequence of a nonautoimmune mechanism.

hOGG1 Ser326Cys polymorphism, interaction with environmental exposures, and gastric cancer risk in Japanese populations.

Oxidative DNA damage caused by reactive oxygen species (ROS) generated by Helicobacter pylori (H. pylori ) infection or smoking may be a cause of gastric cancer development. 8-Hydroxydeoxyguanine (8-OHdG) formation is one of the most common types of oxidative DNA damage, while human oxoguanine glycosylase 1 (hOGG1) is responsible for repairing 8-OHdG lesions. Among several hOGG1 gene polymorphisms, the Ser-->Cys polymorphism at position 326 is related to biological function. To investigate the association between Ser326Cys hOGG1 polymorphism and gastric cancer in relation to the potential risk factors of gastric cancer and antioxidant dietary or nutrient intakes, we conducted a case-control study with 142 histologically-confirmed gastric cancer cases and 271 age, sex-matched healthy controls in Japanese populations. Overall, neither the hOGG1 Ser/Cys nor the Cys/Cys genotype was associated with risk of gastric cancer, compared with the Ser/Ser genotype. A significant interaction was observed between hOGG1 Ser/Cys or Cys/Cys genotype and atrophic gastritis (P for interaction=0.03). No significant interaction was found between hOGG1 genotype and antioxidant dietary or nutrient intakes. The results of the present study suggest that patients with atrophic gastritis in conjunction with the hOGG1 Cys allele might have a higher susceptibility to gastric cancer.

Association of Helicobacter pylori infection and environmental factors in non-cardia gastric cancer in Japan.

BACKGROUND: Although Helicobacter pylori infection is a major risk factor for gastric cancer, it does not explain the full picture of stomach carcinogenesis. There have been few epidemiological studies, however, which examined both H. pylori and environmental factors simultaneously. The aims of this study were to estimate the association of environmental factors (smoking and dietary factors) with gastric cancer in consideration of H. pylori infection, and to investigate the effects of the interaction between environmental factors and H. pylori infection. METHODS: A multicenter, hospital-based, case-control study of gastric cancer was conducted at four hospitals in Nagano prefecture, Japan, between October 1998 and March 2002. For 153 newly diagnosed gastric cancer cases, two controls matched by age (within 3 years), sex, and residence area were randomly selected from the participants of a health check-up program during the same period in the same hospitals. We conducted a questionnaire survey and obtained blood samples. Consequently, 122 non-cardia gastric cancer cases and 235 controls were available for this analysis. RESULTS: Results. H. pylori infection was strongly associated with non-cardia gastric cancer after adjustment for possible confounding factors (odds ratio [OR], 8.2; 95% confidence interval [CI], 3.7-18.2). Cigarette smoking (OR, 2.8; 95% CI, 1.2-6.5) and frequent intake of miso (fermented soy bean) soup (OR, 2.1; 95% CI, 0.9-5.1) and rice (OR, 2.5; 95% CI, 1.0-6.1) were determined to be risk factors even after adjusting for possible confounding factors, including H. pylori infection. However, no statistically significant interaction between environmental factors and H. pylori infection was detected. CONCLUSION: This finding suggests that although H. pylori infection is clearly an important risk factor for gastric cancer, smoking cessation and dietary modification may be practical strategies for the prevention of non-cardia gastric cancer among both H. pylori-positive and -negative subjects in Japan.

Cruciferous vegetables, mushrooms, and gastrointestinal cancer risks in a multicenter, hospital-based case-control study in Japan.

We assessed the possible association of gastrointestinal cancers with cruciferous vegetables and mushrooms in a multicenter, hospital-based case-control study in an agricultural area of Japan. One hundred forty-nine cases and 287 controls for stomach cancer and 115 cases and 230 controls for colorectal cancer were matched by age, sex, and residential area. In stomach cancer, the protective effect of vegetables (consumption of total vegetable) was obscure, but it became clearer when we examined specific kinds of vegetables. Marginal associations were observed in the group of the highest consumption of Chinese cabbage (odds ratio [OR] = 0.61; 95% confidence interval [CI] = 0.35-1.07), broccoli (OR = 0.60; 95% CI = 0.34-1.08), Hypsizigus marmoreus (Bunashimeji) (OR = 0.57; 95% CI = 0.31-1.04) and Pholita nameko (Nameko) (OR = 0.56; 95% CI = 0.30-1.06). In colorectal cancer, we observed decreased risks from the highest tertile of total vegetables (OR = 0.22; 95% CI = 0.08-0.66) and low-carotene-containing vegetables (OR = 0.28; 95% CI = 0.08-0.77), and inverse associations were observed in the group of the highest consumption of broccoli (OR = 0.18; 95% CI = 0.06-0.58). Although the sample size was limited, subgroup analyses showed that the associations differed with the histopathological subtype. These findings suggest that cruciferous vegetables decrease the risk of both stomach and colorectal cancer, and that mushrooms are associated with a decreased risk of stomach cancer.

A novel splice-site variant of the base excision repair gene MYH is associated with production of an aberrant mRNA transcript encoding a truncated MYH protein not localized in the nucleus.

The MYH gene encodes a DNA glycosylase involved in the excision repair of adenines paired with 8-hydroxyguanines, a major component of oxidative DNA damage, and bi-allelic germline MYH mutations have been reported to predispose individuals to multiple colorectal adenomas and carcinoma. To determine whether the MYH gene is involved in gastric carcinogenesis, we examined blood specimens from 20 Japanese familial gastric cancer (GC) patients for MYH mutations by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. Bi-allelic germline MYH mutations were not found in any of the specimens, but in addition to four known variants, a novel splice-site variant, IVS10-2A > G (c.892-2A > G), was found in two patients as its heterozygote. Reverse transcription-PCR analysis revealed that the IVS10-2A > G variant caused the production of an aberrant mRNA transcript encoding a truncated MYH protein. Immunofluorescence analysis showed that the wild-type MYH protein, but not the variant-type, is localized in the nucleus. We then searched for the IVS10-2A > G variant in 128 digestive tract cancer patients by PCR with confronting two-pair primers, and eight cancers from six patients with the IVS10-2A/G genotype were identified. However, no other germline MYH mutations or inactivation of the remaining wild-type allele was detected. We next tested the presumed correlation of the IVS10-2G allele with GC risk in a case-control study of 148 GC cases and 292 controls, but no significant difference in the distribution of the IVS10-2A > G variant was found between the cases and controls. Interestingly, the homozygote for the IVS10-2G allele was found in one GC case, but not in any controls. These results suggested that the ability to repair 8-hydroxyguanine in nuclear DNA may differ among Japanese individuals due to the splicing abnormality based on the MYH IVS10-2A > G variant, and that the bi-allelic IVS10-2A > G variation may be responsible for the occurrence of GC.