Alendronate, a bisphosphonate, increased upper and lower gastrointestinal bleeding: risk factor analysis from a nationwide population-based study.

UNLABELLED: Patients receiving alendronate for osteoporosis carry a significantly higher risk of developing upper gastrointestinal bleeding (GIB) and lower GIB (hazard ratio 1.32 and 1.84, respectively) after adjusting for potential confounding factors such as age, gender, co-morbidity, and some medications. The risk factors associated with GIB were further analyzed. INTRODUCTION: Patients receiving alendronate, a type of bisphosphonate, for osteoporosis have a higher risk of developing upper gastrointestinal bleeding (UGIB). Whether patients receiving alendronate also have a higher risk of lower gastrointestinal bleeding (LGIB) has not been studied. In this study, we investigated the association between GIB and alendronate use and to identify the possible risk factors of GIB among alendronate users. METHODS: Using the National Health Insurance (NHI) Research Database of Taiwan, 3,000 alendronate users and 12,000 age-, sex-, and enrollment time-matched controls were extracted for analysis from a cohort data set of 1,000,000 randomly sampled subjects. Cox proportional hazard regression models were used to identify the risk factors for UGIB and LGIB in all enrollees and alendronate users after adjustments for age, gender, comorbidity (hypertension, diabetes mellitus, coronary heart disease, heart failure, chronic renal disease, chronic obstructive pulmonary disease, peptic ulcer, and cirrhosis), and medications (nonsteroidal anti-inflammatory drugs [NSAIDs], aspirin, steroids, clopidogrel, ticlopidine, warfarin, and selective serotonin reuptake inhibitors). RESULTS: During a median of 1.30-year follow-up, patients receiving alendronate had significant higher risk of UGIB and LGIB after adjusting for age, gender, and potential confounding factors such as comorbidity and medications. Age, chronic renal disease, NSAID, and clopidogrel use may be independent risk factors for UGIB among alendronate users. Age, male gender, clopidogrel, and ticlopidine use may be independent risk factors for LGIB among alendronate users. CONCLUSION: Patients receiving alendronates seemed to carry a higher risk for UGIB and LGIB, respectively, after adjustment for age, sex, underlying comorbidity, and certain medications.

Patients with nonalcoholic fatty liver disease have higher risk of colorectal adenoma after negative baseline colonoscopy.

AIM: The study aimed to determine whether nonalcoholic fatty liver disease (NAFLD) is an independent risk factor of adenoma after negative baseline colonoscopy. METHOD: A retrospective cohort study was conducted on 1522 health-check individuals who underwent two consecutive colonoscopies at Taipei Veterans General Hospital between 2003 and 2010. Those developing an adenoma after an initial negative baseline colonoscopy (adenoma group) were compared with those in whom the second colonoscopy was negative (nonadenoma group). Anthropometric measurements, biochemical tests and the presence of NAFLD were compared between the two groups. RESULTS: The adenoma group had a higher prevalence of NAFLD than the nonadenoma group (55.6% vs 38.8%; P < 0.05). On multivariate logistic regression analysis, NAFLD was an independent risk factor (OR = 1.45, 95% CI: 1.07-1.98) for adenoma formation after a negative baseline colonoscopy. The risk of colorectal adenoma increased when NAFLD patients had other morbidities including metabolic syndrome, hypertension or smoking (OR = 2.85, 4.03 and 4.17). CONCLUSION: NAFLD is an independent risk factor for colorectal adenoma formation after a negative baseline colonoscopy. The risk is higher in individuals with NAFLD and other comorbidities, such as hypertension, smoking or metabolic syndrome.

Impacts of peripheral obestatin on colonic motility and secretion in conscious fed rats.

Obestatin, a novel putative 23-amino acid peptide, was found to be derived from a mammalian preproghrelin gene by using a bioinformatics approach. Although the effects of obestatin on food intake and upper gut motility remain controversial, no studies have been carried out to explore its influence on lower gut motility and secretion. We investigated the impacts of intravenous (IV) injection of obestatin on rat colonic motor and secretory functions. Colonic transit time, fecal pellet output, and fecal content were measured in freely fed, conscious rats, which were chronically implanted with IV and colonic catheters. To test the validity of this animal model, human/rat corticotropin-releasing factor (h/rCRF) served as a stimulatory inducer of colonic motility and secretion. IV injection of obestatin (45, 100, and 300 nmol/kg) did not affect the colonic transit time, whereas IV injection of h/rCRF (30 nmol/kg) effectively accelerated colonic transit time. IV obestatin, in every dose we tested, also did not modify fecal pellet output, frequency of watery diarrhea, total fecal weight, fecal dried solid weight, or fecal fluid weight in the first hour after injection. On the other hand, IV injection of h/rCRF significantly enhanced fecal pellet output, as well as increased the frequency of watery diarrhea, total fecal weight, fecal dried solid weight, and fecal fluid weight during the first hour after injection compared with IV saline controls. In conclusion, peripheral obestatin administration has no impact on colonic motility and secretion in conscious fed rats.

Significance of Rome II-defined functional constipation in Taiwan and comparison with constipation-predominant irritable bowel syndrome.

BACKGROUND: The epidemiology and impact of functional constipation on Asians remain unclear. AIM: To determine the prevalence of functional constipation, its social/medical impact, and its distinction from constipation-predominant irritable bowel syndrome (C-IBS) in Taiwan. METHODS: A Rome II questionnaire was administered to an apparently healthy adult Chinese population (n = 2865). RESULTS: The prevalence of functional constipation was 8.5% and it was 2.7% for C-IBS. The functional constipation subjects were predominantly female and had excessive gastrointestinal-related doctor visits, absenteeism and sleep disturbance compared with controls (P < 0.01). Among functional constipation subjects, approximately 40% were 'consulters' with excessive doctor consultations, absenteeism and sleep disturbance. Female gender, the presence of sleep difficulty and higher constipation symptom scores were predictive of their consultation behaviour (P < 0.05). No differences existed in demographic variables, doctor consultations and absenteeism between 172 functional constipation and 54 C-IBS subjects. However, the C-IBS subjects experienced more severe constipation symptoms and sleep disturbance than functional constipation subjects. CONCLUSIONS: Functional constipation in Taiwan is comparable with that in other countries. The clinical presentation of constipation-predominant irritable bowel syndrome differ somewhat from that of functional constipation.

Differential inhibition of fluid accumulation and tumor growth in two mouse ascites tumors by an antivascular endothelial growth factor/permeability factor neutralizing antibody.

In the accompanying paper (Luo et al., Cancer Res., 58: 2652-2660, 1998), we demonstrated that vascular endothelial growth factor (VEGF), also designated vascular permeability factor (VPF), significantly accumulated in all mouse malignant ascites tested, suggesting its fundamental role in ascites tumors. Removal of VEGF may inhibit the development of ascites tumors. In this study, using a goat antimouse VEGF-neutralizing antibody, we tested this hypothesis with two well-defined syngeneic mouse ascites tumors: MM2 breast adenocarcinoma and OG/Gardner lymphoma 6C3HED (expressing moderate and low levels of VEGF, respectively). This antibody significantly inhibited MM2 and OG cell-free ascites fluid-induced hyperpermeability of mouse peritoneal microvessels and in vitro endothelial cell growth. Mice bearing tumors were administered i.p. daily with the antibody or normal goat IgG as controls for 8 days, at doses of 20-fold (for MM2-bearing mice) or 40-fold (for OG-bearing mice) the estimated amounts of VEGF that kinetically accumulated in the ascites fluid after the tumor inoculation. The average volume of ascites fluid, number of tumor cells and leaked RBCs, and the peritoneal microvessel permeability in MM2-bearing mice that received the antibody treatment were significantly lower than those in the matched controls (P < 0.01). Unexpectedly, OG-bearing mice did not show satisfactory response to the anti-VEGF treatment. This discrepancy was not likely due to inadequate doses or different host immune responses, but it was quite possibly to the different characteristics of MM2 carcinoma and OG lymphoma tumors, the latter being strongly invasive, and/or the existence of an inflammatory mediator(s), such as bradykinin or cytokine(s) other than VEGF. In summary, our results directly demonstrated, for the first time, differential roles for VEGF in ascites tumors in vivo and suggest the potential of VEGF inhibition as a specific therapy for ascites tumors of carcinoma origin, which are the major cause of the malignant ascites in adult humans.

Significant expression of vascular endothelial growth factor/vascular permeability factor in mouse ascites tumors.

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is believed to be a potent mediator of peritoneal fluid accumulation and angiogenesis and of tumor growth in ascites tumor. Such roles, however, have not been generally established because of insufficient quantitative and systemic analyses. To address this, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, 2 lymphomas, 1 leukemia, 1 mastocytoma, and 1 plasmacytoma). Using a newly developed sensitive and specific radioreceptor binding assay and functional assays, we found that active VEGF was significantly accumulated (6-850 ng/ml) in the ascites fluids of all 13 tumors. VEGF concentrations are higher in the tumors of sarcoma and carcinoma origin (430.4 +/- 234.2 ng/ml) than in those of lymphoma and hematological tumor origin (19.2 +/- 10.45 ng/ml). VEGF that accumulated in the peritoneal fluids or expressed in the ascites tumor cells was easily visualized with immunoprecipitation Western blot analysis with a rough correlation to the expression levels of VEGF gene in these tumor cells, suggesting that the tumor cells, at least in part, contributed to the production of the VEGF that accumulated in the ascites fluid. Most ascites tumors expressed VEGF; the 164-amino acid isoform was predominant, the 120-amino acid isoform was less abundant, and the 188-amino acid isoform was least abundant. Several representative ascites tumors expressed similar, if not higher, levels of VEGF when they were cultured at normoxic states, suggesting that they expressed VEGF at high levels in a constitutive manner. The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in normal mice, basically correlated to but did not parallel the VEGF concentrations in their respective ascites fluids. Thus, a complicated relationship may exist between the VEGF production and angiogenesis associated with ascites tumor in vivo. Taken together, our observations suggest that VEGF plays a fundamental role in ascites tumor formation; however, its importance may vary according to tumor origin.

Correlations of chronic hepatitis B virus infection and cigarette smoking with elevated expression of neu oncoprotein in the development of hepatocellular carcinoma.

To investigate the potential role of neu oncogene expression in hepatocarcinogenesis, a nested case-control study was conducted within a cohort of 9691 male adults in Taiwan. Blood samples of study subjects were collected during 1984-1986 and frozen at -30 degrees C until subsequent analysis. The neu oncoprotein level in the stored serum was measured by an enzyme-linked immunosorbent assay for 27 cases of newly developed hepatocellular carcinoma (HCC), 12 liver cirrhosis cases, and 40 healthy controls. The mean level of neu oncoprotein was significantly higher in HCC and liver cirrhosis cases than in controls. The risk of HCC increased significantly with increasing serum level of neu oncoprotein (trend test, P = 0.02). The proportion of subjects having an elevated serum level of neu oncoprotein, defined as a level greater than the mean level of all controls, was significantly higher among asymptomatic HBsAg carriers than noncarriers (P = 0.05), showing a multivariate-adjusted odds ratio of 4.0. Among HCC cases, a strong association was observed between cigarette smoking and elevated prediagnostic serum level of neu oncoprotein. The association remained highly significant (P = 0.017) even when adjustment was made for potential confounders. The multivariate-adjusted odds ratio of having an elevated serum level of neu oncoprotein, defined as a level greater than the mean plus 1 SD of control levels, for HCC cases who smoked more than 10 cigarettes a day was as high as 386.5 compared with the cases who smoked less than 10 cigarettes a day or nonsmoking cases. The results suggest that both HBsAg carrier status and cigarette smoking are related to the increased expression of neu oncogene, and cigarette smoking seems to play a significant role in the latter stages of hepatocarcinogenesis. There was no association between alcohol drinking and serum neu oncoprotein level.

A variant of nuclear localization signal of bipartite-type is required for the nuclear translocation of hypoxia inducible factors (1alpha, 2alpha and 3alpha).

Hypoxia inducible factors (HIF1, 2 and 3), consisting of alpha and beta subunits, play an essential role in various responses to hypoxia. Nuclear entry of alpha subunits is a necessary step for the formation of DNA-binding complex with beta subunit, which is constitutively localized in the nucleus. We show here that the nuclear accumulation of HIF2alpha induced by hypoxia is mediated through a novel variant of bipartite-type nuclear localization signal (NLS) in the C-terminus of the protein, which has an unusual length of spacer sequence between two adjacent basic domains. We further show that when the ubiquitin-proteasome system was deficient or inhibited, HIF2alpha accumulated in the nucleus even under normoxia, also mediated through the bipartite NLS. These findings indicate that the protein stability is critical for the nuclear localization of HIF2alpha and hypoxia is not a necessary factor for the process. Importantly, the NLS of HIF2alpha is also conserved in the other HIF family members, HIF1alpha and HIF3alpha. Mutational analyses proved that the NLS mediating the nuclear localization of HIF1alpha is indeed bipartite-, but not monopartite-type as thought before. Our results suggest that the newly identified NLS is crucial for the functional regulation of HIF family.

Social and medical impact, sleep quality and the pharmaceutical costs of heartburn in Taiwan.

BACKGROUND: Little is known about the social and medical burdens of heartburn in Asia. AIM: To assess the impact of heartburn in Taiwan. METHODS: We applied a questionnaire to 2018 apparently healthy adult Chinese receiving a routine health maintenance programme. Costs of heartburn-related prescriptions were obtained from the Bureau of National Health Insurance of Taiwan. RESULTS: Heartburn prevalence (>1 episode/week) was 7%. Smoking and increased body mass index were associated with heartburn occurrence. Heartburn sufferers reported more atypical gastro-oesophageal reflux disease symptoms, e.g. chest pain, dysphagia and globus. They were more likely to consult physicians, and have an increased frequency and number of days of absenteeism, irrespective of upper gastrointestinal or nongastrointestinal-related illnesses. They experienced sleep disturbances more frequently. The 62 heartburn consulters (48%) were more likely to have co-existing globus, visited physicians more, had more absenteeism, suffered from more sleep disturbances and had higher costs for antacids, proton pump inhibitors, hypnotic/sedatives, tranquilizers and antidepressants than nonconsulters. CONCLUSIONS: Heartburn prevalence in Taiwan is lower than in Western countries. Nevertheless, heartburn in Taiwanese creates a significant burden in terms of social impact, health resource utilization, sleep quality and pharmaceutical costs. The increased costs of psychoactive drugs in consulters suggest that anxiety/depression affects their health-seeking behaviour.

Gender difference on the symptoms, health-seeking behaviour, social impact and sleep quality in irritable bowel syndrome: a Rome II-based survey in an apparent healthy adult Chinese population in Taiwan.

BACKGROUND: Little is known about the gender effect on irritable bowel syndrome in Asia. AIM: To assess the gender difference in Chinese subjects with irritable bowel syndrome meeting Rome II criteria. METHODS: Irritable bowel syndrome was identified from an apparently healthy adult population receiving a routine health maintenance program (n = 2018). RESULTS: Female gender is not a factor associated with irritable bowel syndrome or irritable bowel syndrome-related health care-seeking behaviour. Female irritable bowel syndrome subjects, irrespective of consulting behaviour for irritable bowel syndrome, are likely to have < 3 bowel movements/week, hard/lumpy stools and abdominal fullness/bloating (P < 0.05). Female irritable bowel syndrome subjects are prone to be absent from school/work with more days of absenteeism, irrespective of consultation status (P < 0.05). Only female irritable bowel syndrome consulters have more absenteeism for their irritable bowel syndrome-related symptoms, reporting more sleep disturbances than their male counterparts (P < 0.001). CONCLUSIONS: In an apparent healthy adult population in Taiwan, gender difference is present in Rome II defined Chinese subjects with irritable bowel syndrome as regards bowel symptoms, social impact and sleep quality. Female predominance was not found in irritable bowel syndrome subjects and irritable bowel syndrome-related health care-seeking behaviour in the current population. Both irritable bowel syndrome non-consulters and consulters have similar gender difference profiles in presenting symptoms, suggesting that bowel symptoms per se may not be the only factor leading to health care-seeking behaviour. The gender differences in sleep problems were observed solely in irritable bowel syndrome consulter.

Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study.

BACKGROUND: Controversy exists regarding glucocorticoids therapy and the risk of peptic ulcer bleeding (PUB). AIM: The present study was undertaken to determine whether short-term use of glucocorticoids is associated with the occurrence of peptic ulcer bleeding. METHODS: The records of adult patients hospitalised for newly diagnosed peptic ulcer bleeding from 2000 to 2012 were retrieved from the Taiwan National Health Insurance Research Database, a nationwide population-based registry system. The association between systemic glucocorticoids usage and peptic ulcer bleeding was determined with a conditional logistic regression model comparing cases and controls during time windows of 7, 14 and 28 days using a case-crossover design. RESULTS: Of the 8894 enrolled patients, the adjusted self-matched odds ratios for peptic ulcer bleeding after exposure to the glucocorticoids were 1.37 (95% CI: 1.12-1.68, P = 0.003) for the 7-day window, 1.66 (95% CI: 1.38-2.00, P < 0.001) for the 14-day window and 1.84 (95% CI: 1.57-2.16, P < 0.001) for the 28-day window. Moderate to high, but not low dose glucocorticoids (methylprednisolone <4 mg/day or its equivalence) were associated with an increased risk of peptic ulcer bleeding. Concomitant use of a nonselective nonsteroidal anti-inflammatory drug (NSAID) or aspirin further elevated the risk. However, it does not eliminate the effect of underlying diseases flare-up that may have placed the patients at risk for peptic ulcer bleeding in this kind of study design. CONCLUSIONS: Short-term (7-28 days) exposure to glucocorticoids is significantly associated with peptic ulcer bleeding; this risk seems dose-dependent and is higher when nonselective NSAIDs or aspirin are used concurrently.

erbB-2 and myc oncoproteins in sera and tumors of breast cancer patients.

This study compares the prevalence of elevated serological levels of erbB-2 and myc proteins in 36 breast cancer patients and 25 healthy, ambulatory female controls. The controls were frequency matched to the cases by age and ethnicity. Oncoprotein levels were determined blind to the "case-control status" of the individual from whom the specimen was derived. Corresponding tissue levels were examined in tumors of the 13 cases from whom sufficient tissue was available. Serum oncoproteins were elevated as follows: erbB-2 in one control (4%) compared with nine cases (25%; PFisher's exact = 0.03); myc in no control (0%) compared with seven cases (19%; PFisher's exact = 0.02). Elevated serum levels of erbB-2 or myc oncoproteins were detected in four of the seven cases (57.1%) of in situ cancer without evidence of infiltration. In all cases with elevated serum oncoproteins where tumor tissue was available, the corresponding protein was elevated in the tumor. The three cases who had elevated preoperative serum oncoprotein levels and from whom it was possible to procure postoperative specimens had normal postoperative serum oncoprotein levels. We conclude that (a) erbB-2 and myc oncoproteins are elevated in a proportion of breast cancer patients, (b) the tumor seems to be the source of the serum elevation, and (c) these proteins may be useful as part of a panel of biomarkers of early malignant disease.

A novel gene delivery system targeting cells expressing VEGF receptors.

Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-beta-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with the relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.

Levels of p53 antigen in the plasma of patients with adenomas and carcinomas of the colon.

Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patients enrolled in a colonoscopy study. The mean levels among 47 individuals with normal colonoscopic examinations and no prior history of colonic neoplasia (0.12 ng/ml) and among 61 individuals with normal colonoscopic examinations and a prior history of colonic neoplasia (0.09 ng/ml) were similar. However, the mean levels among 54 individuals with newly diagnosed colonic adenomas (0.44 ng/ml) and 22 individuals with newly diagnosed colonic carcinomas (0.55 ng/ml) were statistically significantly elevated compared to the normal controls (P < 0.02). Among these tumor patients, the plasma levels tended to increase with increasing adenoma size and with increasing carcinoma stage, although these trends were not statistically significant. Defining a significant positive plasma level as any value greater than ten times background, the percentage of positive samples increased from 4% in the controls to 20% in the adenoma cases to 32% in the carcinoma cases. These results demonstrate that plasma p53 protein levels are elevated in a subgroup of individuals with colonic neoplasia.

Occurrence of peptic ulcer disease in connective tissue disease patients associated with xerostomia.

BACKGROUND: Saliva plays a role in mucosal protection and ulcer healing. AIM: : To study whether decreased salivary production leads to peptic ulcer disease in connective tissue disease patients associated with xerostomia. PATIENTS AND METHODS: Two hundred and two connective tissue disease patients (90 with xerostomia and 112 without xerostomia) were enrolled. Their demographic data and use of medications were recorded. Peptic ulcer disease was confirmed by endoscopy. The stimulated salivary output and secretory epidermal growth factor level were measured. RESULTS: Compared with non-xerostomic counterparts, xerostomic patients manifested a higher occurrence of peptic ulcer disease (31% vs. 12%, P = 0.001), lower stimulated salivary output (9.3 +/- 4.1 vs. 22.9 +/- 5.9 mL/15 min, P < 0.001) and lower stimulated salivary epidermal growth factor output (1.40 +/- 0.77 vs. 3.00 +/- 0.96 ng/min, P < 0.001). Multivariate analysis disclosed that an older age (> or = 60 years) (odds ratio, 4.71; P < 0.001), xerostomia with stimulated salivary output of < or =1 mL/min (odds ratio, 7.54; P = 0.014) and the use of non-steroidal anti-inflammatory drugs (odds ratio, 5.76; P = 0.031) were the risk factors leading to peptic ulcer disease. In addition, xerostomic connective tissue disease patients receiving non-steroidal anti-inflammatory drugs manifested an extremely high risk of development of peptic ulcer disease (odds ratio, 19.78; P < 0.001). CONCLUSIONS: Ageing, the use of non-steroidal anti-inflammatory drugs and poor salivary function are potential risk factors for the development of peptic ulcer disease in patients with connective tissue disease. If these xerostomic subjects consume non-steroidal anti-inflammatory drugs, they will encounter an extremely high peptic ulcer disease risk.

The potential risk factors leading to peptic ulcer formation in autoimmune disease patients receiving corticosteroid treatment.

AIM: To study the potential risk factors leading to peptic ulcer disease among autoimmune disease patients on corticosteroid treatment. METHODS: One hundred and thirty-eight corticosteroid-treated autoimmune disease patients were enrolled; their demographic data were recorded and laboratory data were measured. Endoscopy was performed to assess the occurrence of peptic ulcer disease. Helicobacter pylori infection was diagnosed on the basis of rapid urease test and histological examination. RESULTS: Twenty-eight (20%) of 138 autoimmune disease patients had peptic ulcer disease, including 17 with gastric ulcer, eight with duodenal ulcer and three with gastric ulcer plus duodenal ulcer. Eighty five (62%) had used non-steroidal anti-inflammatory drugs and 46 (33%) had H. pylori infection. The majority of peptic ulcer disease subjects showed the following characteristics: age >or= 60 years; male; smokers; non-steroidal anti-inflammatory drug users, particularly the non-specific cyclo-oxygenase inhibitors; presence of hyperpepsinogenaemia I; low H. pylori colonization (P < 0.05). Multivariate analysis revealed that an age >or= 60 years [odds ratio (OR), 6.80; P = 0.001], smoking (OR, 7.94; P = 0.004) and the use of non-specific cyclo-oxygenase inhibitors (OR, 4.71; P = 0.030) were the predominant risk factors for the development of peptic ulcer disease among these patients, whereas H. pylori infection showed a protective role (OR, 0.20; P = 0.022). CONCLUSIONS: Old age, smoking and the use of non-specific cyclo-oxygenase inhibitors are risk factors for peptic ulcer disease in autoimmune disease patients on corticosteroid treatment. H. pylori infection appears to protect against peptic ulcer disease in these patients.

Current patterns of irritable bowel syndrome in Taiwan: the Rome II questionnaire on a Chinese population.

BACKGROUND: Irritable bowel syndrome is a common condition seen in Western countries. In Asia, however, it is less known and even less studied. AIM: To determine the prevalence and social impact of irritable bowel syndrome as well as the health-seeking behaviour of irritable bowel syndrome patients in Taiwan METHODS: Using the modified Rome II questionnaire, a survey was carried out in a population receiving physical check-up (n = 2865). RESULTS: The prevalence of irritable bowel syndrome in Taiwan was 22.1% and 17.5% (kappa = 0.73) according to the Rome II and I criteria, respectively. No gender difference was found between subjects with and without irritable bowel syndrome symptoms. Irritable bowel syndrome subjects were likely to undertake an excessive number of physician-visits (P < 0.01). Such subjects were often absent from work/school, with more days of absenteeism than irritable bowel syndrome-free subjects (P < 0.01). They also suffered obvious sleep disturbance (P < 0.01). Nearly half of the irritable bowel syndrome subjects were 'consulters', and they were more likely to have frequent physician-visits, suffer from work/school absenteeism, and endure sleep disturbance and bowel symptoms than irritable bowel syndrome nonconsulters (P < 0.05). CONCLUSIONS: Irritable bowel syndrome is common in a Chinese population of Taiwan. Similar to irritable bowel syndrome in the West, it also involves significant social and medical burdens. However, in the irritable bowel syndrome subjects of Taiwan there is no gender difference, and more irritable bowel syndrome subjects will seek physician consultations, which may be due to Taiwan's easily accessible and affordable heath care facilities.

Involvement of VEGF and its receptors in ascites tumor formation.

Vascular endothelial growth factor (VEGF) has potent endothelial cell mitotic and vascular permeability activity. Several reports have suggested that VEGF may be one of the major factors regulating ascites formation, although no quantitative and systematic analyses have been carried out. To determine the role of VEGF in ascites formation, we examined the expression of VEGF in 13 mouse ascites tumors (5 sarcomas, 3 carcinomas, and 5 hematopoietic malignancies). We found that significant amounts (6-850 ng/mL) of biologically active VEGF accumulated in the ascites fluid of all 13 tumors, particularly in tumors of sarcoma and carcinoma origin (430 +/- 234 ng/mL). The microvessel densities in the peritoneal walls of tumor-bearing mice, which are significantly higher than those in healthy mice, basically correlated with but did not parallel VEGF concentrations, suggesting the existence of an additional modulator(s) of the angiogenic process. Administration of anti-mouse VEGF-neutralizing antibody to mice bearing the carcinoma-derived ascites tumor MM2 suppressed ascites accumulation, tumor growth, and tendency to bleed. These results directly demonstrate the crucial role of VEGF in carcinoma-derived ascites tumor formation in vivo.

Clinical, virological, and pathological significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C.

PURPOSE: Hepatic bile duct injuries are characteristic histological findings in patients with chronic hepatitis C virus (HCV) infection. However, the pathogenesis and clinical significance of this phenomenon remain unclear. The aims of this study were to evaluate the prevalence and clinical significance of hepatic bile duct injuries in Chinese patients with chronic hepatitis C. METHODS: One hundred and seventeen Chinese patients with chronic hepatitis C were enrolled. Clinical, biochemical, immunological (serum autoantibodies and cryoglobulinemia), histological, and virological data (serum HCV RNA titer and HCV genotype) were compared between patients with and without hepatic bile duct injuries. RESULTS: Eighty-three (71%) of the 117 patients with chronic hepatitis C had hepatic bile duct injuries. Patients with hepatic bile duct injuries had a significantly higher frequency of HCV genotype 1b; a higher mean serum globulin level; significantly higher mean scores for histological periportal necro-inflammation, portal inflammation, and fibrosis; and more severe portal lymphoid aggregation/follicles when compared with patients without hepatic bile duct injuries (P < 0.05, all). No significant differences in the presence of serum autoantibodies, cryoglobulinemia, mean serum HCV RNA titer, or response to interferon treatment were noted between the two groups. Multivariate logistic regression analysis showed that HCV genotype 1b infection, portal inflammation, and lymphoid aggregation/follicles were significant independent predictors associated with hepatic bile duct injuries. CONCLUSIONS: The presence of hepatic bile duct injuries in Chinese patients with chronic hepatitis C was significantly correlated with HCV genotype 1b infection, and the patients with these injuries had more severe portal inflammation and formation of lymphoid aggregates/follicles.