Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer.

OBJECTIVE: To investigate the frequency and integrity of certain cag pathogenicity island genes (cagPAI) in Helicobacter pylori strains and their association with peptic ulcer disease (PUD) and gastric cancer. MATERIAL AND METHODS: We enrolled 240 adult patients [120 with functional dyspepsia (FD), 50 with PUD and 70 with gastric cancer] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed when either culture or any two of the three tests (rapid urease test, histopathology and specific ureA PCR) were positive. DNA extracted from H. pylori isolates and positive gastric tissues were tested by PCR for the presence of different genes of cagPAI using specific primers. RESULTS: A total of 122 (51%) patients were H. pylori positive. Frequencies of cagPAI genes cagA, cagE, cagT and cagM in H. pylori strains from different groups of patients were as follows: functional dyspepsia 73, 83, 76 and 60%, PUD 70, 94, 91, 70% and gastric cancer 75, 95, 90 and 70%, respectively. Risk associated for the presence of PUD and gastric cancer with cagPAI genes cagE, cagT and cagM was 5.0-, 4.6- and 4.1- and 3.0-, 2.8- and 2.5-folds, respectively. Prevalence of intact cagPAI was significantly higher in PUD and gastric cancer compared to functional dyspepsia (PUD vs. functional dyspepsia, 71% vs. 38%, P = 0.01; gastric cancer vs. functional dyspepsia, 75% vs. 38%, P < 0.01). Intact cagPAI was associated with increased risk for the presence of PUD (odds ratio 5.2, 95% CI 2.4-11.3) and for the presence of gastric cancer (odds ratio 4.5, 95% CI 2.3-7.1). CONCLUSIONS: cagPAI integrity and its different genes are linked to different forms of gastric disease and so may have a role in pathogenesis, diagnosis and management.

Identification of opportunistic enteric parasites among immunocompetent patients with diarrhoea from Northern India and genetic characterisation of Cryptosporidium and Microsporidia.

PURPOSE: Enteric parasitic infestation is a major public health problem in developing countries. Parasites such as Cryptosporidium spp., Cyclospora spp., Cystoisospora spp. and Microsporidia may cause severe diarrhoea among immunocompromised patients. There is scanty data on their frequency among immunocompetent patients. Accordingly, we studied the frequency of enteric opportunistic parasites among immunocompetent patients with diarrhoea from northern India; we also performed genetic characterisation of Cryptosporidia and Microsporidia among them. PATIENTS AND METHODS: Stool samples from 80 immunocompetent patients with diarrhoea, and 110 healthy controls were examined. Parasites were detected by direct microscopy, modified acid-fast (Kinyoun's) and modified trichrome stain. Polymerase chain reaction--restriction fragment length polymorphism was used for genetic characterisation of selected species such as Cryptosporidia and Microsporidia. RESULTS: Enteric parasites were detected in 16/80 (20%) patients (mean age 28.8±20 years, 45, 56% males) and in 2/110 (1.8%) healthy controls (P=0.00007). Parasites detected were Cryptosporidium spp. (8/16, 50.0%), Cystoisospora spp. (4/16, 25%), Microsporidia (1/16, 6.25%), Cyclospora spp. (1/16, 6.25%) and Giardia spp. (1/16, 6.25%). One patient had mixed infection with Cystoisospora spp. and Giardia spp. The species of Cryptosporidia and Microsporidia detected were Cryptosporidium hominis and Enterocytozoon bieneusi, respectively. Parasites were more often detected in younger patients (≤20 years of age) than in older. Most of the parasite infected patients presented with chronic diarrhoea. CONCLUSION: Opportunistic enteric parasitic infestation was more common among immunocompetent patients with diarrhoea than healthy subjects. Special staining as well as molecular methods are essential for appropriate diagnosis of these parasites.

Intestinal microsporidiosis in renal transplant recipients: Prevalence, predictors of occurrence and genetic characterization.

PURPOSE: Intestinal microsporidiosis, which occurs in immunocompromised states such as acquired immunodeficiency syndrome, has rarely been studied in patients with renal transplantation (RT) on immunosuppressive therapy. MATERIALS AND METHODS: Three hundred and twenty-four consecutive RT recipients on immunosuppressive treatment and 170 healthy subjects were evaluated for intestinal microsporidiosis and other parasites by modified trichrome staining, wet mount using normal saline, iodine and polymerase chain reaction (PCR). Clinical, demographic and laboratory parameters associated with occurrence of intestinal microsporidiosis were studied using univariate and multivariate analysis. The species of microsporidia were studied using PCR-restriction fragment length polymorphism (RFLP). Patients were treated with albendazole (400 mg twice daily for 2 weeks). RESULTS: Of 324 RT recipients initially screened, 52 were excluded from final analysis due to incomplete data. Patients with RT [n=272, age 42±12.54 years, 222 (81.6%) male] more often had microsporidiosis than healthy subjects by modified trichrome stain and PCR [n=170, age 33.8±6.7 years, 123 (72.3%) male] [16/272 (5.8%) vs. 0/170 (0%), P<0.001]. Patients with intestinal microsporidiosis were younger (33.9±8.3 years vs. 42.3±12.6 years; P=0.009), had diarrhoea more often (13/16, 81% vs. 123/256, 48%; P=0.02), which was longer in duration (60, 32.5-105 days vs. 12, 6.2-18 days; P<0.001) and had associated giardiasis (2/16, 12.5% vs. 2/256, 0.8%; P=0.018). Younger age, presence of diarrhoea and associated giardiasis were significant on multivariate analysis. Enterocytozoon bieneusi was detected in 15/16 (93%) patients with intestinal microsporidiosis. CONCLUSION: Intestinal microsporidiosis occurs frequently in patients with RT on immunosuppressive treatment, particularly among younger patients with longer diarrhoea duration and associated giardiasis. E. bieneusi is the major species identified among these patients.

Dynamic article: composite antropyloric valve and gracilis muscle transposition for total anorectal reconstruction: a preliminary report.

BACKGROUND: Technique and functional outcomes of anorectal reconstruction using an antropyloric graft have been reported previously. This technique had reasonable initial outcomes but lacked voluntary function. OBJECTIVE: We hereby report the initial results of patients who underwent gracilis muscle wrapping around the perineally transposed antropyloric valve in an attempt to improve voluntary fecal control. SETTING: This study was conducted at a single tertiary care institution. PATIENTS: Eight adult patients (7 men and 1 woman) with a median age of 38 years (range, 19-51 years) underwent this procedure. Seven patients already had anorectal reconstruction with a transposed antropyloric valve, and 1 patient with severely damaged anal sphincter complex underwent single-stage composite antropylorus transposition with a gracilis muscle wrap. MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and functional status of the composite graft in the perineum. RESULTS: No operative mortality or serious procedure-related morbidity occurred in any patient. The median postoperative resting pressure was 29 mmHg (range, 22-38 mmHg) and squeeze pressure was 72.5 mmHg (range, 45-267 mmHg). There was a significant improvement in the squeeze pressure following surgery (p = 0.039). Also, the St. Mark's incontinence scores significantly improved in all patients and varied between 7 and 9 (p = 0.003). The ability to defer defecation and the reduced frequency of leakage accidents were the prime reasons for improved postgraciloplasty outcomes in these patients. On personal interviews, all patients who underwent this procedure were satisfied with the results of their surgery. LIMITATIONS: A longer follow-up with a larger sample size is required. Quality-of-life data have not been evaluated in this study. CONCLUSIONS: Gracilis muscle wrapping around a perineally transposed antropyloric valve is possible and improves the voluntary control and overall functional outcomes in a select group of patients with end-stage fecal incontinence requiring anal replacement (Supplemental Digital Content 1, http://links.lww.com/DCR/A173).

A cross-cultural investigation of attachment style, catastrophizing, negative pain beliefs, and symptom severity in irritable bowel syndrome.

BACKGROUND: Little information exists regarding whether psychosocial variables in irritable bowel syndrome (IBS) vary by geographic location. Adult attachment is an important psychological concept rooted in childhood relationship experience that has not been previously studied in IBS. Catastrophizing and negative pain beliefs have been described in IBS and may be affected by attachment. AIMS: In this cross-cultural study, we determined: (i) whether attachment differs between IBS patients and controls, (ii) whether geographic location has a significant effect on attachment style, catastrophizing and negative pain beliefs, and (iii) how all three variables correlate with IBS symptom severity. METHODS: 463 IBS patients, with moderate to severe symptom scores, and 192 healthy controls completed validated questionnaires about attachment, catastrophizing, negative pain beliefs and IBS-SSS in nine locations, USA (New York, Los Angeles), Mexico, Italy (Rome, Bari), Romania, Iran, India, and China. KEY RESULTS: Attachment anxiety and avoidance scores were significantly higher in IBS patients than in controls (p < 0.001). This was particularly true for the fearful-avoidant attachment category, especially in China and Romania. Path analysis showed that attachment anxiety and avoidance had indirect effects on IBS-SSS through catastrophizing (p < 0.0001) and negative pain beliefs (p = 0.005). All three psychosocial measures varied significantly depending on location. CONCLUSIONS & INFERENCES: In the IBS population studied, attachment style was significantly different in IBS compared to a control population. Geographic differences in attachment, catastrophizing and negative pain beliefs were documented and their correlation with symptom severity and thus, research of psychosocial variables in IBS should take into account the location of the population studied.

Conducting multinational, cross-cultural research in the functional gastrointestinal disorders: issues and recommendations. A Rome Foundation working team report.

BACKGROUND: Cross-cultural, multinational research can advance the field of functional gastrointestinal disorders (FGIDs). Cross-cultural comparative research can make a significant contribution in areas such as epidemiology, genetics, psychosocial modulators, symptom reporting and interpretation, extra-intestinal co-morbidity, diagnosis and treatment, determinants of disease severity, health care utilisation, and health-related quality of life, all issues that can be affected by geographical region, culture, ethnicity and race. AIMS: To identify methodological challenges for cross-cultural, multinational research, and suggest possible solutions. METHODS: This report, which summarises the full report of a working team established by the Rome Foundation that is available on the Internet, reflects an effort by an international committee of FGID clinicians and researchers. It is based on comprehensive literature reviews and expert opinion. RESULTS: Cross-cultural, multinational research is important and feasible, but has barriers to successful implementation. This report contains recommendations for future research relating to study design, subject recruitment, availability of appropriate study instruments, translation and validation of study instruments, documenting confounders, statistical analyses and reporting of results. CONCLUSIONS: Advances in study design and methodology, as well as cross-cultural research competence, have not matched technological advancements. The development of multinational research networks and cross-cultural research collaboration is still in its early stages. This report is intended to be aspirational rather than prescriptive, so we present recommendations, not guidelines. We aim to raise awareness of these issues and to pose higher standards, but not to discourage investigators from doing what is feasible in any particular setting.

A four-country comparison of healthcare systems, implementation of diagnostic criteria, and treatment availability for functional gastrointestinal disorders: a report of the Rome Foundation Working Team on cross-cultural, multinational research.

BACKGROUND: Variations in healthcare provision around the world may impact how patients with functional gastrointestinal disorder (FGIDs) are investigated, diagnosed, and treated. However, these differences have not been reviewed. PURPOSES: The Multinational Working Team of the Rome Foundation, established to make recommendations on the conduct of multinational, cross-cultural research in FGIDs, identified seven key issues that are analyzed herein: (i) coverage afforded by different healthcare systems/providers; (ii) level of the healthcare system where patients with FGIDs are treated; (iii) extent/types of diagnostic procedures typically undertaken to diagnose FGIDs; (iv) physicians' familiarity with and implementation of the Rome diagnostic criteria in clinical practice; (v) range of medications approved for FGIDs and approval process for new agents; (vi) costs involved in treating FGIDs; and (vii) prevalence and role of complementary/alternative medicine (CAM) for FGIDs. Because it was not feasible to survey all countries around the world, we compared a selected number of countries based on their geographical and ethno-cultural diversity. Thus, we included Italy and South Korea as representative of nations with broad-based coverage of healthcare in the population and India and Mexico as newly industrialized countries where there may be limited provision of healthcare for substantial segments of the population. In light of the paucity of formal publications on these issues, we included additional sources from the medical literature as well as perspectives provided by local experts and the media. Finally, we provide future directions on healthcare issues that should be taken into account and implemented when conducting cross-cultural and multinational research in FGIDs.

Associations between IL-1RA polymorphisms and small intestinal bacterial overgrowth among patients with irritable bowel syndrome from India.

BACKGROUND: Low-grade inflammation (controlled by pro and anti-inflammatory molecules), induced by gut microbes in patients with small intestinal bacterial overgrowth (SIBO), may be associated with irritable bowel syndrome (IBS). Polymorphisms of IL-RA gene (anti-inflammatory) was evaluated in IBS and healthy subjects (HS); small intestinal mucosal IL-1α and ß levels (pro-inflammatory) in relation to the presence of SIBO were evaluated in a subset of patients. METHODS: Two hundred and twenty-one IBS patients and 273 age- and gender-matched HS were included. Exactly 209 of 221 patients (Rome III) and 273 HS were genotyped (PCR) for IL-1RA polymorphism. Mucosal IL-1α and ß levels (pg/mg of biopsy) were estimated (ELISA) in 82/221 patients with and without SIBO (≥10(5)  CFU/mL upper gut aspirate bacteria). KEY RESULTS: Genotype 1/1 (IL-1RA over-producer) was less frequent among patients than controls (p = 0.007); genotypes 1/3 (p = 0.012, OR = 3.301, 95% CI = 1.31-8.35) and 2/3 (both under-producers; p = 0.009, OR = 7.703, 95% CI = 1.66-35.82) were commoner among IBS. Fifteen of 82 (18.3%) patients had SIBO. Levels of IL-1α and ß were higher among patients with SIBO than without (IL-1α: 35.4 [20.1-66.8] vs 25.5 [4.2-65.3], p < 0.001; IL-1ß: 206.8 [133.5-365.9] vs 93.1 [25.5-197.7], p < 0.001) and those with bloating than without (p = 0.012; p = 0.015). IL-1ß was higher among patients with Bristol stool type 6 than those with type 1-2 (p = 0.002) and type 3-5 (p = 0.007). CONCLUSIONS & INFERENCES: Polymorphisms 1/1 (IL-1RA over-producer) was infrequent and 1/3 and 2/3 (under-producers) frequent among IBS. Increased IL-1α and ß levels were associated with SIBO. Increased IL-1ß level was predominantly associated with bloating and loose stools (Bristol type 6).

Neurovascular antropylorus perineal transposition using inferior rectal nerve anastomosis for total anorectal reconstruction: preliminary report in humans.

BACKGROUND: Technical feasibility of inferior rectal nerve anastomosis to the anterior vagus branch of the perineally transposed antropyloric valve for total anorectal reconstruction has been previously demonstrated in cadavers. To the best of our knowledge, the present study is the first report of using this procedure in humans. METHODS: Eight patients [mean age 35.5 years (range 15-55 years); (male/female = 7:1)] underwent the procedure. The antropyloric valve with its anterior vagus branch was mobilized based on the left gastroepiploic arterial pedicle. The antral end was anastomosed to the distal colon. The anterior vagus nerve was anastomosed by epineural technique to the inferior rectal nerve in the perineum. A diverting proximal colostomy was maintained for 6 months. Anatomical integrity of the graft (on magnetic resonance imaging scans), its arterial pedicle (on computed tomography angiogram) and neural continuity (on ultrasound and pyloric electromyography) were assessed. Functional assessment was performed using barium retention studies, endoscopy, manometry and fecal incontinence scores. RESULTS: Tension-free end-to-end anastomosis of the anterior vagus nerve to the right (n = 7) and left (n = 1) inferior rectal nerve was achieved. An intact left gastroepiploic pedicle, a healthy graft and neural continuity were visualized on perineal ultrasound. Electromyographic activity was noticed on neural stimulation. Endoscopy and barium studies showed voluntary antral contraction and contrast retention, respectively, in all patients. The mean resting and squeeze pressures were 26.25 mmHg (range 16-62 mmHg) and 50.25 mmHg (range 16-113 mmHg), respectively. St. Mark's incontinence scores varied between 7 and 12. There were no major surgical complications. CONCLUSIONS: Pudendal (inferior rectal) innervation of the perineally transposed antropylorus in total anorectal reconstruction is feasible and may improve outcomes in selected patients with end-stage fecal incontinence.

Perineal antropylorus transposition for end-stage fecal incontinence in humans: initial outcomes.

BACKGROUND: Technical feasibility of perineal antropyloric valve transposition to reconstruct a severely damaged incontinent anal sphincter or to replace an excised anorectal sphincter has been reported previously. OBJECTIVE: This study aimed to document the follow-up results of patients who underwent successful perineal antropyloric valve transposition for end-stage fecal incontinence. SETTING: This study was conducted at a single tertiary care institution. PATIENTS: Seventeen patients underwent the procedure. Eight patients had replacement (group 1) and 9 patients had augmentation (group 2) of the anal sphincter. Two patients in group 1 with early graft-related complications were excluded from further analysis, because they had the grafts excised. MAIN OUTCOME MEASURES: The primary outcome measures were anatomical integrity and functional status of the graft in the perineum, fecal incontinence scores, and quality-of-life scores (SF-36) over a median follow-up of 18 months. RESULTS: The transposed grafts had a definite tone on digital examination, were well visualized on perineal MRI, showed high-velocity vascular inflow on Doppler ultrasound study, and good vascularity on celiac CT angiography. Anal manometry showed a significant (p = 0.03) rise in the postoperative resting neosphincter pressures with good retention of barium proximal to pyloric valve on distal loopogram. The postoperative St Mark incontinence score improved in both groups and was significantly better in group 2 than in group 1. There was significant improvement in postoperative physical and mental component scores in both groups with higher scores in group 2 than in group 1 on follow-up. LIMITATIONS: A longer follow-up with a larger sample size is required. CONCLUSIONS: Antropyloric valve transposition can be used effectively for a selected group of patients with end-stage fecal incontinence. Patients undergoing anal sphincter augmentation have better outcomes in comparison with those having an excised sensate anorectum.

Expression profile of latent and lytic transcripts of epstein-barr virus in patients with gastroduodenal diseases: a study from northern India.

Epstein-Barr virus (EBV) has been shown to be associated with gastric cancer. However, inconsistent findings have been reported regarding the EBV reactivation in gastric cancer and non-carcinomatous gastric epithelium. Therefore, the aim of the study was to investigate the effect of clinicopathological findings on the expression of different transcripts of EBV in patients with gastric cancer, peptic ulcer, and dyspepsia. A total of 200 adult patients (dyspepsia [120], peptic ulcer [30], gastric cancer [50]) undergoing upper gastrointestinal endoscopy were enrolled. EBV infection was diagnosed with non-polymorphic Epstein-Barr nuclear antigen1 (EBNA1) gene based PCR and confirmed by real-time PCR. The transcripts of EBV were detected by real-time RT-PCR. In patients with gastric cancer and peptic ulcer, EBV DNA was detected more often than in those with dyspepsia (P < 0.05). EBNA1 transcript was detected in all EBV positive cases and its expression was neither associated with disease nor with histopathological findings. The expression of BZLF1 was significantly associated with gastric cancer and peptic ulcer compared to dyspepsia (P < 0.01). BZLF1 expression was also found to be higher in Helicobacter pylori infected patients (P = 0.058). Expression of BARF1 and BcLF1 were significantly higher in gastric epithelium of patients having severe grade chronic inflammation (P = 0.05) and gastric atrophy (P = 0.02), respectively. In conclusion, increased expression of lytic transcripts in patients with gastric cancer, peptic ulcer, gastric atrophy, chronic inflammation and H. pylori infection suggests the association of these factors with EBV reactivation.

Quantitation of Helicobacter pylori ureC gene and its comparison with different diagnostic techniques and gastric histopathology.

Numerous diagnostic assays for Helicobacter pylori detection are available. However, these techniques have their own advantages as well as limitations. Here we tried to develop a real-time quantitative (Q) PCR assay to measure ureC copy number to detect H. pylori, based on the fact that there is only one copy of the ureC gene per bacterium. We enrolled 120 adult patients [non-ulcer dyspepsia (NUD) 60, peptic ulcer disease (PUD) 20, gastric cancer (GC) 40] undergoing upper gastrointestinal endoscopies. During each endoscopic examination, antral biopsies from normal region of the antrum were obtained and subjected to the following tests: RUT, culture, histopathology, H. pylori-specific ureC PCR and ureC Q-PCR. Calculation of H. pylori copy number was based on the standard curve generated using 10-fold dilutions of DNA extracted from the H. pylori control strain varying from 10(5) to 10(1) copies. The prevalence of H. pylori infection in our study population was 54% with no significant difference among disease and control population. The sensitivity of Q-PCR was found to be 100% which was highest among all diagnostic tests. The established Q-PCR is around 10 times more sensitive than the conventional PCR method. The copy number of H. pylori DNA was significantly increased when overall gastritis, H. pylori density, chronic inflammation and intestinal metaplasia were present. In summary, we developed a rapid and sensitive Q-PCR method for detecting H. pylori. This technique offers a significant improvement over other available methods for detecting H. pylori in clinical and research samples.

Virulence attributes of Helicobacter pylori isolates & their association with gastroduodenal disease.

BACKGROUND & OBJECTIVES: Certain genotype(s) of Helicobacter pylori strains may play important role in the development of gastric cancer (GC) and peptic ulcer disease (PUD). This study was undertaken to investigate the association of cagA, cagA3/ region subtypes, babA2 and vacA genotypes of H. pylori with GC, PUD and non-ulcer dyspepsia (NUD) as there are no such studies from India. METHODS: A total of 348 consecutive adult patients (NUD 241, PUD 45, GC 62) undergoing upper gastrointestinal endoscopy between September 2002 and May 2007 in a tertiary referral centre at Lucknow, north India, were enrolled. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. Genotyping for cagA, cagA3/ subtypes, babA2 and vacA was performed by PCR using sequence specific primers. RESULTS: H. pylori infection was higher in patients with PUD than with GC (80 vs. 56.5%, P < 0.01) and NUD (80 vs. 55.2%, P= 0.002). cagA positive H. pylori isolates were detected in 80 per cent in GC, 83.3 per cent in PUD and 76.7 per cent in NUD with no significant difference among them. Only A subtype of cagA3/ was detected and its distribution in GC, PUD and NUD was 68.8, 69.4 and 52.6 per cent respectively. Presence of babA2 genotype was 31.4 per cent and it had significant association with PUD when compared with NUD (52.8 vs. 26.3%, P<0.003). On univariate regression analysis, s1a allele was associated with GC (P<0.050) and s1a/m2 vacA genotype with both GC (P=0.014) and PUD (P=0.016). INTERPRETATION & CONCLUSIONS: H. pylori infection was strongly associated with PUD with a very high proportion of patients with GC have s1a allele and s1a/m2 vacA genotype. Both s1a/m2 vacA genotype and babA2 are associated with PUD. The study shows that different virulence attributes of H. pylori are involved in different gastroduodenal disorders.

Analysis of Pro12Ala PPAR gamma polymorphism and Helicobacter pylori infection in gastric adenocarcinoma and peptic ulcer disease.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-dependent transcription factor involved in various disease processes including inflammation and carcinogenesis. We investigated the association of Pro12Ala PPARgamma polymorphism and Helicobacter pylori infection with gastric cancer and peptic ulcer disease (PUD). PATIENTS AND METHODS: In total, 348 adult patients [62 gastric adenocarcinoma, 45 PUD and 241 nonulcer dyspepsia (NUD)] who underwent an upper gastrointestinal endoscopy were enrolled. PPARgamma polymorphism was analyzed by PCR-based restriction fragment length polymorphism. H. pylori infection was diagnosed by rapid urease test, culture, histopathology and PCR. RESULTS: PPARgamma G carrier had significant association with gastric adenocarcinoma [P = 0.023, odds ratio (OR) = 2.136, 95% CI = 1.112-4.104] and PUD (P = 0.028, OR = 2.165, 95% CI = 1.008-4.306) when compared with NUD. Combination of G carrier and H. pylori infection further increased the risk of gastric adenocarcinoma (OR = 3.054, 95% CI = 1.195-7.807) and PUD (OR = 11.161, 95% CI = 3.495-35.644). PPARgamma polymorphism did not increase the risk of gastric adenocarcinoma and PUD in H. pylori-negative subjects. CONCLUSIONS: The study suggests that Pro12Ala PPARgamma polymorphism is associated with gastric adenocarcinoma and PUD, and is a potential marker for genetic susceptibility to these two diseases in the presence of H. pylori infection.

Anti-Saccharomyces cerevisiae antibody is not useful to differentiate between Crohn's disease and intestinal tuberculosis in India.

CONTEXT: Clinical, endoscopic, radiological and histological parameters of intestinal tuberculosis (IT) and Crohn's disease (CD) are so similar that differentiation between these two diseases, which require different treatment, is difficult. Anti- Saccharomyces cerevisiae antibody (ASCA), which is often present in the sera of patients with CD, may be potentially useful to differentiate CD from IT. AIM: To evaluate the role of enzyme-linked immunosorbent assay test for ASCA in serum in differentiating CD from intestinal tuberculosis. SETTINGS AND DESIGN: Prospective case-control study. MATERIALS AND METHODS: Sixteen patients with IT, 16 CD, 36 UC diagnosed using standard parameters and 12 controls (11 healthy subjects and one with colonic carcinoma) were tested for IgG ASCA in serum. STATISTICAL ANALYSIS USED: Categorical variables were analyzed using Chi-square test with Yates' correction, as applicable. Continuous variables were analyzed using Mann-Whitney U test. RESULTS: Eight of 16 (50%) patients with IT, 10 of 16 with CD (62%), nine of 35 with UC (26%) and one of 12 controls tested positive for ASCA in serum. Though the frequency of ASCA in serum was comparable among patients with IT and CD (8/16 vs. 10/16, P = ns), IT and UC (8/16 vs. 9/35, P =ns), CD and UC (10/16 vs. 9/35, P =ns), its frequency in CD or IT but not in UC was higher than healthy controls (P Conclusions: Serum ASCA is unlikely to be useful to differentiate between CD and IT in India.

Association of genetic polymorphisms of N-acetyltransferase 2 and susceptibility to esophageal cancer in north Indian population.

Esophageal cancer is multifactorial disease involving environmental and genetic risk factors. Tobacco smoke and alcohol are strong environmental risk factors. N-acetyltransferase 2 (NAT2) is known to metabolize heterocyclic amine carcinogens in tobacco smoke. The purpose of this study was to determine whether genetic polymorphism in the NAT2 and their interaction with environmental factors influence the susceptibility for esophageal cancer. For our study, 126 patients and 164 controls were genotyped for NAT2 2 * 5, 2 * 6 and 2 * 7 polymorphisms using PCR-RFLP method. In a case-control study, NAT2 slow acetylator genotype was not significantly associated with risk of esophageal cancer (OR 1.3, 95%CI = 0.78-2.2, P = 0.28). There was significant linkage disequilibrium between 2 * 5-2 * 6 and 2 * 5-2*7 (P < 0.05). Using expectation maximization algorithm, 6 haplotypes were obtained but none of them revealed any significant contribution to disease susceptibility. In case only analysis, the smokers with rapid acetylator were at slightly higher risk of esophageal cancer (OR 1.3, 95%CI = 0.62-3.0, P = 0.43) which was not statistically significant. NAT2 slow or fast genotypes did not affect the risk of esophageal cancer in patients with alcohol consumption or occupational exposure. These results suggest that NAT2 acetylator genotypes did not influence the susceptibility to esophageal cancer. NAT2 polymorphism did not significantly modulate the cancer risk after interaction with environmental factors like tobacco, alcohol or occupational exposure.

Cytokine gene polymorphisms and the pathology of chronic gastritis.

INTRODUCTION: Helicobacter pylori (H. pylori) infection is associated with divergent clinical outcomes and these outcomes are largely influenced by the levels of cytokines in the gastric mucosa. The levels of these cytokines are dependant on cytokine gene polymorphisms. Pro-inflammatory cytokine polymorphisms are strongly associated with severe histological changes in the gastric mucosa in Caucasian populations. METHODS: In this study, we evaluated the role of cytokine gene polymorphisms in influencing the pathological severity of gastritis. 120 patients were evaluated. Cytokine gene polymorphisms of interleukin-1 (IL-1) beta, tumour necrosis factor alpha and the IL-1 receptor antagonist genes were done using polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR variable number of tandem repeats markers typed on the deoxyribonucleic acid obtained from the peripheral blood. Histological analysis was done by using the revised Sydney system. RESULTS: There was no association between pro-inflammatory cytokine gene polymorphisms and severity of gastritis. CONCLUSION: This data suggests that high cytokine levels are not seen in the gastric mucosa in Indians in spite of H. pylori colonisation. IL-1 beta is a potent proinflammatory cytokine which causes a partial clearance of the organism as well as hypochlorhydria. Corporal hypochlorhydria causes a persistent colonisation by H. pylori followed by the development of gastric atrophy and later carcinoma. This lack of association with a pro-inflammatory polymorphism suggests that only low levels of IL-1 beta are present in the gastric mucosa. This causes a low clearance of the organism and a high incidence of duodenal ulceration because of hyperchlorhydria. However, it is protective against the development of gastric carcinoma. This would explain the "Indian Paradox" of the apparent discrepancy of a high degree of colonisation by H. pylori and a low incidence of gastric carcinoma in the Indian population.

Aggressive angiomyxoma of the jejunum: a rare cause of obscure gastrointestinal bleeding.

Obscure gastrointestinal bleeding accounts for nearly 5% of all gastrointestinal haemorrhage and is frequently due to a lesion in the small bowel. We report the case of a male patient with obscure overt gastrointestinal bleed in whom repeated upper gastrointestinal endoscopy, colonoscopy, computed tomography scanning and exploratory laparotomy showed no specific pathology. However, on capsule endoscopy done subsequently, a small polyp in the jejunum was located and resected. Histology revealed an aggressive angiomyxoma. This type of small bowel lesion has not been reported in the literature before.

Gastroduodenal dysmotility in patients with gallbladder carcinoma: frequency of occurrence and clinical importance.

BACKGROUND: Gastric stasis, common in patients with gall-bladder carcinoma (GBC), results from anatomical obstruction or motor abnormalities. We studied patients with GBC for antroduodenal motor dysfunction using manometry. METHODS: Forty-one patients with GBC without endoscopic gastric outlet obstruction and 10 healthy controls were evaluated using a symptom scoring system for gastric stasis, saline load test and water perfusion antroduodenal manometry. Fasting, post-prandial and post-octreotide motility were recorded and analysed on a computer using GiPC manometry software. RESULTS: Sixteen of 41 patients (39%) with GBC reported recurrent vomiting; patients with vomiting had a higher symptom score (13 [11-17] v. 6 [4-10], p<0.0001] and higher volume of aspirate on the saline load test (460 ml [210-650] v. 160 ml [70-260], p<0.0001) as compared with those without vomiting. Healthy subjects more often had spontaneous fasting migratory motor complex than patients with GBC (9/10 v. 13/41, p=0.002). The amplitudes of contractions in the antrum and duodenum were significantly lower in patients with GBC than in healthy subjects. Patients with GBC had lower fasting (157 [68-284] v. 190.5 [150-284], p=0.01) and post-prandial (200 [96-395] v. 284 [178-395], p<0.0001) antral motor indices than healthy subjects. Patients with GBC and vomiting had significantly lower contraction amplitude and motility indices than those without vomiting. Motility indices correlated inversely with the symptom score and volume of aspirate on the saline load test (Spearman correlation, p = 0.01 for all). CONCLUSION: Antroduodenal motor abnormalities are common in patients with GBC. These may explain the symptoms of gastric stasis and abnormal results of the saline load test in the absence of anatomical obstruction in such patients.