Helicobacter pylori outer membrane protein and virulence marker differences in expatriate patients.

We studied the prevalence of Helicobacter pylori virulence markers, e.g. cytotoxin associated gene (cagA), cagA promoter, vacuolating associated cytotoxin A (vacA) alleles induced by contact with epithelium (iceA type), and outer membrane protein Q (hopQ) in expatriates and compared them with those in local residents. Gastric biopsies were obtained at endoscopy for culture, histology and PCR for virulence marker and hopQ. Of 309 patients, 236 (76%) were males with a mean age of 45 years. A total of 102 patients were expatriates. hopQ type 1 was present in 98 (47%) local residents compared to 88 (86%) expatriates (P < 0·001), while hopQ type 2 was present in 176 (85%) local residents, compared to 60 (59%) expatriates (P < 0·001). H. pylori virulence marker cagA was positive in 97 (47%) local residents compared to 86 (84%) expatriates (P < 0·001) while cagA-P was positive in 72 (35%) local residents compared to 87 (85%) expatriates (P < 0·001). iceA type 1 was positive in 157 (76%) local residents compared to 45 (44%) expatriates (P < 0·001), while iceA type 2 was positive in 81 (39%) local residents compared to 86 (84%) expatriates (P < 0·001). Distribution of H. pylori cagA, cagA promoter, iceA and hopQ type in local residents and expatriates was different. H. pylori virulence markers were associated with severe pathology in expatriates.

Virulence markers of Helicobacter pylori in patients with diarrhoea-dominant irritable bowel syndrome.

Recent studies suggest that irritable bowel syndrome (IBS) is associated with low-grade inflammation. This study aims to determine the distribution of Helicobacter pylori cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) alleles (e.g., s1 and s2) in patients with diarrhoea-dominant IBS (IBS-D) as the latter causes vacuolation in colonic epithelial cells in vitro. One hundred and seventy patients meeting Rome III criteria for IBS-D (mean age: 40 +/- 15 years) were enrolled. Gastric biopsy was assessed histologically and DNA extraction was performed by polymerase chain reaction (PCR) for H. pylori genus 16S ribosomal DNA (16S rDNA), cagA and vacA allele s1 and s2. There was no age- or gender-related difference in H. pylori positivity in IBS-D compared to the control group. H. pylori was positive in 116 (68%) with IBS-D compared to 88 (55%) in the control group (P=0.01). cagA was positive in 73 (63%) with IBS-D compared to 42 (48%) in the control group (P=0.03). vacA s1 was positive in 61 (53%) with IBS-D compared to 32 (36%) in the control group (P=0.02). cagA s1 was positive in 39 (34%) with IBS-D compared to 13 (15%) in the control group (P=0.002).

Entamoeba species associated with chronic diarrhoea in Pakistan.

We determined the prevalence of Entamoeba (E.) histolytica, E. dispar and E. moshkovskii in patients with chronic diarrhoea associated with abdominal pain or discomfort mimicking irritable bowel syndrome. Stool samples were collected from 161 patients with chronic diarrhoea and from 157 healthy controls. Stool microscopy with modified trichrome stain, culture and polymerase chain reaction (PCR) for Entamoeba spp. differentiation was performed. Microscopy demonstrated Entamoeba cysts in 44% (57/129) of patients with diarrhoea compared to 29% (44/151) of controls (P=0·009). In patients with diarrhoea, PCR for E. histolytica was positive in 9% (11/129) (P=0·008), E. dispar in 19% (24/129) (P=0·117) and E. moshkovskii in 19% (24/129) (P<0·001). E. histolytica and E. moshkovskii were significantly associated with diarrhoea while E. dispar was found equally in both groups.

Microsporidial infections due to Encephalitozoon intestinalis in non-HIV-infected patients with chronic diarrhoea.

We determined the prevalence of microsporidia Enterocytozoon (Ent.) bieneusi and Encephalitozoon (E.) intestinalis infection in patients with chronic diarrhoea and hepatocellular carcinoma (HCC). A total of 330 stool samples were examined from 171 (52%) patients with chronic diarrhoea, 18 (5%) with HCC while 141 (43%) were controls. Stool microscopy, polymerase chain reaction (PCR) with species-specific primers for Ent. bieneusi and E. intestinalis and sequencing were carried out. Microsporidia were found by trichrome staining in 11/330 (3%) and E. intestinalis by PCR in 13/330 (4%) while Ent. bieneusi was not detected. PCR for E. intestinalis was positive in 8/171 (5%) stool samples from patients with chronic diarrhoea, 2/141 (1·4%) samples from healthy controls and in 3/18 (17%) samples from patients with HCC. In the chronic diarrhoea group, E. intestinalis was positive in 4/171 (2·3%) (P=0·69) stool samples compared to 2/18 (11%) (P=0·06) in the HCC group and 2/141 (1·4%) from healthy controls. E. intestinalis infection was significantly associated with chronic diarrhoea and HCC in these patients who were negative for HIV. Stool examination with trichrome or species-specific PCR for microsporidia may help establish the cause of chronic diarrhoea.

Helicobacter pylori: association with gall bladder disorders in Pakistan.

Helicobacter species colonise the biliary tract and therefore this study explores the relationship between of Helicobacter pylori and cholecystitis. Bile and gall bladder tissue samples were obtained from 144 patients who underwent cholecystectomy. Of these, 89 had chronic cholecystitis with cholelithiasis, 44 had gall bladder carcinoma and 11 had gall bladder polyps. Histopathology examination included special staining and immunohistochemistry (IHC), while Helicobacter species (H. pylori, H. bilis and H. hepaticus) were detected by the polymerase chain reaction (PCR). Sequencing and BLAST query of PCR products was undertaken and samples were considered to contain H. pylori if both PCR and IHC were positive. Immunohistochemistry for H. pylori was positive in 22 (25%) cases compared to five (9%) in the control group (P=0.02). Testing (PCR) for 16S rDNA was positive in 23 (26%) cases compared to six (11%) controls (P=0.03). Negative PCR results were obtained for H. bilis and H. hepaticus. Twenty-four (89%) were positive by both 16S rDNA PCR and IHC for H. pylori (P<0.001). Both PCR for 16S rDNA and IHC were positive in 21 (24%) cases compared to five (9%) controls (P=0.03). Sequencing of 16S rRNA and glmM PCR products were consistent with H. pylori. In conclusion, H. pylori DNA was demonstrated in cases of chronic cholecystitis and gall bladder carcinoma associated with cholelithiasis, but this association requires further study.

Is full colonoscopic examination necessary in young patients with fresh bleeding per rectum?

BACKGROUND AND STUDY AIMS: Guidelines and practices differ regarding evaluation of young patients with fresh bleeding per rectum (FBPR). The aim of this study was to determine the frequency and site of endoscopic lesions in young patients with FBPR, and to thereby determine whether full colonoscopic examination is necessary in these patients. METHODS: Consecutive patients aged 18-50 years who were scheduled to undergo full colonoscopy for FBPR at Aga Khan University Hospital between May 2007 and October 2009 were enrolled in the study after giving informed consent. FBPR was defined as the passing of fresh blood per rectum with or without stools and/or noticing blood in the toilet bowl. Lesions were characterized as proximal or distal to the splenic flexure. Patients with positive family history of colorectal cancer, bleeding requiring blood transfusion, bleeding diathesis, or iron deficiency anemia were excluded. RESULTS: A total of 379 patients met the inclusion criteria and were analyzed. Of these, 248 patients (65.4%) were under 40 years of age and 131 (34.6%) were aged 40-50 years. Mean hemoglobin was 12.93 ± 1.78 g/dL. In patients < 40 years, seven (2.8%) adenomatous polyps and malignant lesions were found, all of which were located in the distal colon. In patients aged 40-50 years, 10 (7.6%) adenomatous polyps and malignant lesions were detected, one of which was located in the proximal colon. On univariate analysis, malignant and adenomatous lesions were significant in the 40-50 years age group (P = 0.031; OR, 2.84; 95% CI 1.05-7.65). CONCLUSION: Endoscopic lesions in patients younger than 40 years with FBPR are found mostly in the distal colon and hence flexible sigmoidoscopy seems to be a reasonable evaluation tool in young patients with no other alarm symptoms.

Health care risk factors among women and personal behaviours among men explain the high prevalence of hepatitis C virus infection in Karachi, Pakistan.

To estimate the prevalence and identify factors associated with hepatitis C virus (HCV) infection among men and women in Karachi, Pakistan. We conducted a cross-sectional study of adult men and women in a peri-urban community of Karachi (Jam Kandah). Households were selected through systematic sampling from within all villages in the study area. All available adults within each household were interviewed about potential HCV risk factors. A blood specimen was collected to test for anti-HCV antibodies by enzyme immunoassay. We used generalized estimating equations while accounting for correlation of responses within villages to identify the factors associated with HCV infection. Of 1997 participants, 476 (23.8%) were anti-HCV positive. Overall, HCV infection was significantly associated with increasing age, ethnicity, and having received > or =2 blood transfusions, > or =3 hospitalizations, dental treatment and >5 injections among women. Among women, > or =2 blood transfusions [adjusted odds ratio (aOR) = 2.32], >5 injections during the past 6 months (aORs = 1.47), dental treatment (aOR = 1.31) and increasing age(aOR = 1.49), while among men, extramarital sexual intercourse (aOR = 2.77), at least once a week shave from barber (aOR = 5.04), > or =3 hospitalizations (aOR = 2.50) and increasing age (aOR = 1.28) were associated with HCV infection. A very high prevalence of HCV was found in the study population. Among women, unsafe health care practices, while among men extramarital sex, shaving from a barber and hospitalizations were associated with HCV infection. Efforts are needed to improve the safety of medical procedures to reduce the transmission of HCV in Pakistan [Corrections made in Summary after initial online publication.].

Low prevalence of the intact cag pathogenicity island in clinical isolates of Helicobacter pylori in Karachi, Pakistan.

Clinical diseases that follow Helicobacter pylori infection are associated with expression of the cagA gene, a part of cytotoxin-associated gene pathogenicity island (cag-PAI). This study aims to determined whether or not the presence of cagA is associated with the presence of complete cag-PAI and to evaluate inflammatory changes associated with the five loci in the cag-PAI of H. pylori comprising cagA, cagA promoter region (cagAP), cagE, cagT and the left end of the cagA gene (LEC). H. pylori isolates were obtained from patients with dyspeptic symptoms. Clinical strains of H. pylori were screened by the polymerase chain reaction (PCR) for respective genes of the cag-PAI. Of 115 H. pylori isolates, 31 (28%) were positive for the five cag-PAI loci. H. pylori isolates with intact cag-PAI were associated with gastric carcinoma (GC; n=9 [60%]) and gastric ulcer (GU; n=5 [45%]) compared to non-ulcer dyspepsia (NUD; n=14 [18%]) (P=0.001 and P=0.049, respectively). In patients with intact cag-PAI, acute on chronic inflammation was present in 25 (81%) and was more common than chronic inflammation (P=0.013). The cagE and cagAP had deletions in 25 (37%) and 23 (35%) cases, respectively. The cagAP region was significantly associated with GC (n=12 [80%], P<0.001) and GU (n=9 [82%], P=0.001) compared to NUD (n=24 [30%] and with significant acute on chronic inflammation (n=40 [80%], P=0.007). The distribution of vacAs1a with intact cag-PAI in GC was 9 (60%) and in NUD was 10 (13%) (P<0.001). The presence of the cagA gene does not signify presence of an intact cag-PAI. Most of the H. pylori isolates studied had partial cag-PAI with missing cagE and cagA promoter regions.

Medical mortality in Pakistan: experience at a tertiary care hospital.

AIM: To acquire systematic data on the causes of hospital mortality in Pakistan, a developing country with scant mortality records. STUDY DESIGN: Retrospective review of death certificates and hospital charts of patients dying on general and specialty medical services at our hospital during one calendar year. RESULTS: Of a total 10,590 admissions, 657 (6.2%) died in hospital. The deceased included 357 (54.4%) males and 299 (45.6%) females, with a collective median age of 63 years and mean length of stay 6.71 days (median 4 days, range 1-56 days). Primary cause of death was categorised as infectious (21.2%), pulmonary (17.2%), cancer related (15.7%), cardiovascular (12.6%), gastrointestinal and hepatic (10.8%), neurological (11.4%) and miscellaneous (11.1%). Within each category, the most common diagnoses were septicaemia (76.9% of infectious cases), pneumonia (55.7% of pulmonary cases), myocardial infarction (40.9% of cardiovascular), intracranial haemorrhage (37.3% of neurological), and cirrhosis (45.0% of gastrointestinal). There were multiple causes among malignant disorders with no single cause dominating. Patients with cardiovascular and pulmonary deaths tended to be older than the median age (p = 0.001), while patients with gastrointestinal and cancer related deaths tended to be younger than the median age (p = 0.001). Length of stay did not differ significantly among the various subgroups. About a quarter (26.4%) deaths occurred within 24 h of admission. CONCLUSIONS: Infections, including septicaemia and pneumonia, are the leading causes of hospital mortality in our setting, followed by malignancy and cardiovascular causes. The overall mortality rate is comparable to published mortality data from other hospital settings.

Granulomatous gastritis: a diagnostic dilemma?

Granulomatous inflammation of the gastrointestinal tract is an uncommon entity; an aetiopathogenic diagnosis can be reached only by combining the morphological examination with clinical and laboratory investigations. We report two cases of granulomatous gastritis: a 27-year-old woman presenting with weight loss and a 55-year-old woman presenting with epigastric pain and vomiting. Upper oesophagastroduodenoscopy in these cases showed antral hyperaemia and histopathology showed non-caseating gastric granulomatous inflammation. Both the cases were extensively worked-up for possible tuberculosis (TB) as the patients lived in an endemic area, before starting steroids for the possibility of Crohn's disease (CD) . The first patient improved but the second patient had a flare of underlying undiagnosed TB. Granulomatous gastritis present a diagnostic challenge for treating physicians because of similar clinical, laboratory and endoscopical features between CD and intestinal TB.

Endoscopic retrograde cholangiopancreaticography with or without stenting in patients with pancreaticobiliary malignancy, prior to surgery.

BACKGROUND: Postoperative morbidity and mortality are high in patients undergoing pancreatico-duodenectomy for malignant pancreatico-biliary stricture. Different approaches have been tried to improve the outcomes, including pre-surgical biliary stenting with endoscopic retrograde cholangiopancreaticography (ERCP). OBJECTIVES: To assess the beneficial and harmful effects of biliary stenting via ERCP for pancreatico-biliary stricture confirmed or suspected to be malignant, prior to surgery. SEARCH STRATEGY: We identified trials through The Cochrane Hepato-Biliary Group Controlled Trials Register (October 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 2, 2006), MEDLINE (1950 to October 2006), EMBASE (1980 to October 2006), and Science Citation Index Expanded (1945 to October 2006). We also searched the references in the published papers and wrote to stent producers. SELECTION CRITERIA: Randomised trials comparing ERCP with biliary stenting versus ERCP without biliary stenting for pancreatico-biliary malignancy prior to surgery. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials for inclusion and extracted data. The primary pre-surgical, post-surgical, and final outcome measures were mortality. The secondary outcomes were complications such as cholangitis, pancreatitis, bleeding, pancreatic fistula, intra-abdominal abscess, improvement in bilirubin, and quality of life. Dichotomous outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) based on fixed- and random-effect models. MAIN RESULTS: We identified two randomised trials with 125 patients undergoing pancreatico-duodenectomy; 62 patients underwent ERCP with biliary stenting and 63 had ERCP without biliary stenting prior to surgery. Pre-surgical mortality was not significantly affected by stenting (OR 3.14, 95% CI 0.12 to 79.26), while there were significantly more complications in the stented group (OR 43.75, 95% CI 2.51 to 761.8). Stenting had no significant effect on the post-surgical mortality (OR 0.75, 95% CI 0.25 to 2.24). However, post-surgical complications were significantly less in the stented group (OR 0.45, 95% CI 0.22 to 0.91). Overall mortality (OR 0.81, 95% CI 0.17 to 3.89) and complications (OR 0.50, 95% CI 0.01 to 23.68) were not significantly different in the two groups. AUTHORS' CONCLUSIONS: We could not find convincing evidence to support or refute endoscopic biliary stenting on the mortality in patients with pancreatico-biliary malignancy. Large randomised trials are needed to settle the question of pre-surgical biliary stenting.

Gastric variceal bleed in a patient without liver cirrhosis: an unusual cause of haematemesis.

Tumours of the pancreas presenting as haematemesis are rare entities, with scarce documentation in literature. We report a 50-year-old woman who presented with haematemesis secondary to gastric fundal variceal bleeding due to splenic vein occlusion by a large mucinous cystadenoma of the pancreas. We also review the literature pertaining to unusual pathologies presenting as haematemesis.

Mucormycosis in patients with complicated cirrhosis.

INTRODUCTION: Rhino-orbito-cerebral mucormycosis is a rapidly progressive and fatal disease that mostly occurs in patients with diabetes mellitus and immunocompromised status. Antifungal therapy with surgical debridement is the standard of care. Patients with cirrhosis of liver are more prone to develop different infections. Many of these also show glucose intolerance or frank diabetes mellitus. Little is known about the clinical presentation and outcome of mucormycosis in patients with cirrhosis. Treatment is difficult due to underlying coagulopathy and hepatic dysfunction. METHODS: Medical records of the past five years were searched for the cirrhotic patients admitted with associated diagnosis of mucormycosis or fungal infection. Six patients with mucormycosis were identified. RESULTS: Out of six patients, five were male. Age range was 15-57 years. Cause of cirrhosis was hepatitis C in four patients, hepatitis B in one patient and autoimmune hepatitis in one patient. Two patients had hepatocellular carcinoma. Four patients had diabetes mellitus, of which one patient was also on steroids for the autoimmune liver disease. Four patients had spontaneous bacterial peritonitis at the time of admission. All six patients presented with rhino-orbitocerebral mucormycosis with nasal discharge and upper motor neuron signs. Diagnosis of mucormycosis was made by culture of biopsy and scrapings taken from the palate and nasal sinuses. These patients received amphotericin B. Four patients died while in the hospital, while two patients died within next few days after discharge. CONCLUSION: Mucormycosis in cirrhosis is not very common and has a poor prognosis. Patients with advanced cirrhosis and diabetes mellitus are at risk of developing infection.

Comparison of biopsy-based methods for the detection of Helicobacter pylori infection.

Various biopsy-based methods for the detection of Helicobacter pylori are evaluated to determine their sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), followed by polymerase chain reaction (PCR) for the 16S ribosomal RNA (rRNA) gene of H. pylori (16S PCR) to confirm the results. Seventyfive patients (65% [49] males, age range: 17-77 years, mean 42+/-14.6 years) with dyspeptic symptoms are included in the study. Gastric antrum biopsy specimens collected during endoscopy are tested using a urea agar base enriched with 40% urea solution (eUAB, Oxoid)), a commercial rapid urease test (Pronto Dry, Medical Instrument Corp, Switzerland), histopathology and 16S PCR. The eUAB test showed 97% sensitivity, 86% specificity, 84% PPV, 97% NPV and 91% accuracy when the diagnosis of H. pylori infection was made with positive Pronto Dry and histopathology. Pronto Dry showed 100% sensitivity, 82% specificity, 80% PPV, 100% NPV and 89% accuracy when the diagnosis of H. pylori infection was made on positive histopathology and eUAB. Thus, the eUAB can be used as a rapid urease test. It is economical and has a sensitivity and specificity comparable to a commercially available rapid urease test to detect urease activity of H. pylori in gastric biopsy.

Thymosin alpha 1 in combination with interferon alpha and ribavirin in chronic hepatitis C patients who are non-responders or relapsers to interferon alpha plus ribavirin.

OBJECTIVE: Interferon alpha (IFN-alpha) with or without ribavirin is an approved therapy for patients with chronic hepatitis C. However, a sustained response is achieved in less than 40% of all treated cases. Retreatment of relapsers or non-responders usually fails. Thymosin alpha 1 (Ta-1) is a polypeptide with immunomodulatory properties that has been suggested to increase response rates in patients with chronic hepatitis C. The aim of present study was to evaluate the efficacy of a novel triple regimen which includes Ta-1 for relapsers and non-responders to the combination of TA-1 and ribavirin. METHODS: In the present study, 11 patients who relapsed (n=5) or did not respond (n=6) to previous INF-alpha-based therapy were retreated with combination Ta-1, INF-alpha and ribavirin for 12 months, and followed up for a further six months. RESULTS: Four out of five relapsers had a sustained response. One of the non-responders cleared the HCV RNA during the post-treatment follow-up. Minor adverse effects were observed during treatment with this combination therapy and no dose reduction or discontinuations were needed. CONCLUSION: This data suggests that thymosin alpha 1 may add to the efficacy of INF-alpha plus ribavirin in the retreatment of relapsers or non-responders to previous INF-alpha-based hepatitis C therapy.

Survival data and prognostic factors seen in Pakistani patients with esophageal cancer.

BACKGROUND: Esophageal cancer is common in Pakistan. An attempt has been made for the first time to look at the survival data and prognostic factors associated with esophageal cancer in this region. PATIENTS AND METHODS: We did a retrospective review of 263 cases seen at the Aga Khan University Hospital in Karachi. Data analysis was done using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: Squamous cell carcinoma was noted in 81% of the cases, whereas adenocarcinoma was the second most common. At the time of diagnosis, early-stage disease was found in 25%, locally advanced in 41% and metastatic in 34% of all cases. Mean age at diagnosis was 56 years, with 59% males and 41% females. Survival data were available in 89 cases. Median survival was 7 months. On univariate analysis, the following factors were of prognostic significance: obstruction, histology, albumin level at diagnosis, age and platelet count. On multivariate analysis, three factors were found prognostic: presence or absence of obstruction, squamous cell carcinoma versus adenocarcinoma and platelet count. CONCLUSIONS: We found that patients with squamous cell carcinoma and absence of thrombocytopenia and obstruction had a better overall survival. However, this is a limited retrospective analysis; we therefore recommend that these prognostic factors be evaluated in larger studies.