Abdulrahman M Aljebreen

LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency

BACKGROUND Clinical immunology has traditionally relied on accurate phenotyping of the patients immune dysfunction for the identification of a candidate gene or genes for sequencing and molecular confirmation. Although this is also true for other branches of medicine, the marked variability in immune-related phenotypes and the highly complex network of molecules that confer normal host immunity are challenges that clinical immunologists often face in their quest to establish a specific genetic diagnosis. OBJECTIVE We sought to identify the underlying genetic cause in a consanguineous family with chronic inflammatory bowel disease-like disorder and combined immunodeficiency. METHODS We performed exome sequencing followed by autozygome filtration. RESULTS A truncating mutation in LPS-responsive beige-like anchor (LRBA), which abolished protein expression, was identified as the most likely candidate variant in this family. CONCLUSION The combined exome sequencing and autozygosity mapping approach is a powerful tool in the study of atypical immune dysfunctions. We identify LRBA as a novel immunodeficiency candidate gene the precise role of which in the immune system requires future studies.

Differentiating Intestinal Tuberculosis From Crohn's Disease: A Diagnostic Challenge

With the changing epidemiology of Crohns disease (CD) and intestinal tuberculosis (ITB), we are in an era where the difficulty facing physicians in discriminating between the two diseases has increased, and the morbidity and mortality resulting from a delayed diagnosis or misdiagnosis is considerably high. In this article, we examine the changing trends in the epidemiology of CD and ITB, in addition to clinical features that aid in the differentiation of both diseases. The value of various laboratory, serological, and the tuberculin skin tests are reviewed as well. The use of an interferon-γ-release assay, QuantiFERON-TB Gold, in the workup of these patients and its value in populations where the bacillus Calmette–Guérin vaccine is still administered is discussed. Different radiological, endoscopic, and pathological similarities and features that can aid the clinician in reaching a rapid diagnosis are reviewed as well. The association between mycobacteria and CD, the concerns with the practice of antituberculosis medication trials in areas where tuberculosis (TB) is endemic, as well as extrapulmonary TB induced by the use of antitumor necrosis factor-α agents are delineated in this article. Furthermore, we propose an algorithm for the investigation of patients in whom the differential diagnosis encompasses CD and ITB.

Clinico-pathological patterns of colorectal cancer in Saudi Arabia: younger with an advanced stage presentation.

AIM Colorectal cancer (CRC) is the third most common cancer in the world. The aim of this study was to identify the clinical and pathological features of CRC in a tertiary care hospital in Saudi Arabia. MATERIALS AND METHODS This is a retrospective study of all patients diagnosed to have CRC at King Khalid University Hospital in Riyadh, Saudi Arabia over a 10 year period (1995-2005). The data collected from medical files, endoscopy and imaging reports included age, gender, clinical presentation, smoking, relevant past or family history, site and size of the tumor, stage, carcinoembryonic antigen level and tumor grade. RESULTS A total of 113 patients were included over the 10 year period. The average age at diagnosis was 55 years (S.D.=15), 58% of the patients were males and 42% were females. Thirty-seven percent of the patients were 50 years of age or younger. The most common clinical presentation was abdominal pain (68%) followed by rectal bleeding (62%) and weight loss (55%). Left-sided lesions and rectal cancer constituted 76% and 48% of all CRC tumors respectively. Sixty-eight percent of lesions were stage C and above. Forty-five percent of patients presented with complete large bowel obstruction. CONCLUSION In this analysis, we found that Saudi patients were more likely to present with colorectal cancer at a more advanced stage of the disease and at younger ages compared to Western populations. This data suggests the need for a mass screening program to be implemented for this common and preventable cancer in Saudi Arabia.

Sedation-risk-free colonoscopy for minimizing the burden of colorectal cancer screening.

Unsedated colonoscopy is available worldwide, but is not a routine option in the United States (US). We conducted a literature review supplemented by our experience and expert commentaries to provide data to support the use of unsedated colonoscopy for colorectal cancer screening. Medline data from 1966 to 2009 were searched to identify relevant articles on the subject. Data were summarized and co-authors provided critiques as well as accounts of unsedated colonoscopy for screening and surveillance. Diagnostic colonoscopy was initially developed as an unsedated procedure. Procedure-related discomfort led to wide adoption of sedation in the US, although unsedated colonoscopy remains the usual practice elsewhere. The increased use of colonoscopy for colorectal cancer screening in healthy, asymptomatic individuals suggests a reassessment of the burden of sedation in colonoscopy for screening is appropriate in the US for lowering costs and minimizing complications for patients. A water method developed to minimize discomfort has shown promise to enhance outcomes of unsedated colonoscopy. The use of scheduled, unsedated colonoscopy in the US appears to be feasible for colorectal cancer screening. Studies to assess its applicability in diverse practice settings deserve to be conducted and supported.

Prospective study of endoscopic ultrasound performance in suspected choledocholithiasis.

Background:  The close proximity of the echoendoscope to the extrahepatic bile ductal system and its safety make endoscopic ultrasonography (EUS) an excellent method for examining the common bile duct (CBD). The aim of the present study was to compare EUS diagnostic performance for CBD stones with endoscopic retrograde cholangiography (ERC).

Seroprevalence of celiac disease among healthy adolescents in Saudi Arabia

AIM To identify the seroprevalence of celiac disease among healthy Saudi adolescents. METHODS Between December 2007 and January 2008, healthy students from the 10(th) to 12(th) grades were randomly selected from three regions in Saudi Arabia. These regions included the following: (1) Aseer region, with a student population of 25512; (2) Madinah, with a student population of 23852; and (3) Al-Qaseem, with a student population of 16067. Demographic data were recorded, and a venous blood sample (5-10 mL) was taken from each student. The blood samples were tested for immunoglobulin A and immunoglobulin G endomysial antibodies (EMA) by indirect immunofluorescence. RESULTS In total, 1167 students (614 males and 553 females) from these three regions were randomly selected. The majority of the study population was classified as lower middle class (82.7%). There were 26 (2.2%) students who had a positive anti-EMA test, including 17 females (3.1%) and 9 males (1.5%). Al-Qaseem region had the highest celiac disease prevalence among the three studied regions in Saudi Arabia (3.1%). The prevalence by region was as follows: Aseer 2.1% (10/479), Madinah 1.8% (8/436), and Al-Qaseem 3.2% (8/252). The prevalence in Madinah was significantly lower than the prevalence in Aseer and Al-Qaseem (P = 0.02). CONCLUSION Our data suggest celiac disease prevalence might be one of the highest in the world. Further studies are needed to determine the real prevalence.

Prevalence and clinical features of colonic diverticulosis in a Middle Eastern population

AIM To determine the prevalence, location, associations and clinical features of colonic-diverticulosis and its role as a cause of lower-gastroenterology-bleeding. METHODS We retrospectively reviewed the medical records of 3649 consecutive patients who underwent a colonoscopy for all indications between 2007 and 2011 at King Khalid University Hospital, Riyadh, Saudi Arabia. The demographic data were collected retrospectively through the hospitals information system, electronic file system, endoscopic e-reports, and manual review of the files by two research assistants. The demographic information included the age, sex, comorbidities and indication for the colonoscopy. The association among colonic polyps, comorbidities and diverticular disease was also measured. RESULTS A total of 270 patients out of 3649 were diagnosed with colonic diverticulosis, with a prevalence of 7.4%. The mean age was 60.82 years ± 0.833, (range 12-110). Females comprised 38.89% (95%CI: 33-44.7) of the study population. The major symptoms were rectal bleeding in 33.6%, abdominal pain in 19.3%, constipation in 12.8% and anemia in 6%. Diverticula were predominantly left-sided (sigmoid and descending colon) in 62%, right-sided in 13% and in multiple locations in 25%. There was an association between the presence of diverticulosis and adenomatous polyps (P-value < 0.001), hypertension (P-value < 0.0001) and diabetes mellitus (P-value < 0.0016). Diverticular disease was the second most common cause of lower gastrointestinal bleeding, in 33.6% (95%CI: 27.7-39.4), after internal hemorrhoids, in 44.6% (95%CI: 40.3-48.9). On multivariable logistic regression, hypertension (OR = 2.30; 95%CI: 1.29-4.10), rectal bleeding (OR = 2.57; 95%CI: 1.50-4.38), and per year increment in age (OR = 1.05; 95%CI: 1.03-1.07) were associated with diverticulosis but not with bleeding diverticular disease. LIMITATIONS A small proportion of the patients included had colonoscopies performed as a screening test. CONCLUSION Colonic-diverticulosis was found to have a low prevalence, be predominantly left-sided and associated with adenomatous-polyps. Age, hypertension and rectal bleeding predict the presence of diverticular disease.

Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

BACKGROUND Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. MATERIALS AND METHODS TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the C-1306T SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. RESULTS AND CONCLUSIONS The MMP-2 C-1306T SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 C-1306T SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

New insights into gastrointestinal and hepatic granulomatous disorders

Numerous diseases that involve the gastrointestinal tract reveal the presence of granulomas on histological analysis. Granulomatous diseases can be either primary or secondary to environmental factors. Granulomas are dynamic structures composed of organized collections of activated macrophages, including epithelioid and multinucleated giant cells, surrounded by lymphocytes. The formation of granulomas is usually in response to antigenic stimulation and is orchestrated through cytokines, immune cells and host genetics. In this Review, the pathogenesis and etiologies of granulomas of the gastrointestinal tract and liver are discussed, as are the available diagnostic tools to help differentiate their various underlying etiologies. In addition, the role of granulomas in harboring latent tuberculosis is reviewed. The effects of tumor necrosis factor antagonists and interferon-α on the development of granulomas are also discussed.

Seroprevalence rates of Helicobacter pylori and viral hepatitis A among adolescents in three regions of the Kingdom of Saudi Arabia: is there any correlation?

Background:  The seroprevalence rate of Helicobacter pylori in the Kingdom of Saudi Arabia (KSA) was reported to be in the range of 50–80% among mostly symptomatic patients in non‐community‐based studies. However, the seroprevalence of viral hepatitis A (HAV) underwent a marked decline in the last two decades from over 50% in 1989 to 25% in 1997 among Saudi children under the age of 12 years. The aim of this paper was to study seroprevalence rates of H. pylori and HAV among the adolescent population in three regions of KSA and to determine whether there was any correlation between them.