Habeb A.M.,Prince Mohammed Bin Abdulaziz Hospital |
Habeb A.M.,Endocrine and Diabetes Unit |
Deeb A.,Mafraq Hospital |
Johnson M.,University of Exeter |
And 11 more authors.
Hormone Research in Paediatrics | Year: 2015
Background: Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 mutations and characterized by early-onset diabetes and skeletal dysplasia. Hepatic dysfunction has been reported in 60% of patients. Aims: To describe a cohort of WRS patients and discuss the pattern and management of their liver disease. Methods: Detailed phenotyping and direct sequencing of EIF2AK3 gene were conducted in all patients. Results: Twenty-eight genetically confirmed patients (67% male; mean age 4.6 years) were identified. 17 different EIF2AK3 mutations were detected, of which 2 were novel. The p.S991N mutation was associated with prolonged survival and p.I650T with delayed onset. All patients presented before 25 months with diabetes with variation in the frequency and severity of 10 other features. Liver disease, first manifested as non-autoimmune hepatitis, was the commonest extra-pancreatic feature identified in 85.7% (24/28). 22/24 had at least one episode of acute hepatic failure which was the cause of death in all deceased patients (13/28). One child was treated by liver transplantation and had no liver disease and better diabetes control for the following 6 years. Conclusions: Liver disease in WRS is more frequent than previously described and carries high mortality. The first experience with liver transplantation in WRS is encouraging. © 2015 S. Karger AG, Basel.
Bastaki J.M.,Sabah Hospital |
Bastaki J.M.,Kuwait Cancer Control Center |
Purgina B.M.,University of Ottawa |
Dacic S.,University of Pittsburgh |
Seethala R.R.,University of Pittsburgh
Head and Neck Pathology | Year: 2014
Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary gland malignancy. While currently designated as an adenocarcinoma, myoepithelial differentiation has been implied in previously reported cases. We herein perform a survey of our cases of signet ring cell adenocarcinoma and review the literature in order to refine categorization of this rare tumor. Five cases were retrieved. One was reclassified as a mammary analogue secretory carcinoma, leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the presence of prominent signet ring or vacuolated cells arranged in islands, interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools of mucin. An extensive panel of histochemical and immunohistochemical stains and fluorescence in situ hybridization (FISH) (modeled after common phenotypes and molecular alterations seen in signet ring and myoepithelial tumors at other sites) was performed. The male-to-female ratio was 3:1. The mean age was 56 years (range 18-81). Sites involved included buccal mucosa (2), soft palate (1) and deep parotid (1). Perineural and angiolymphatic invasion were present in three and two cases respectively. One patient was lost to follow up and the remainder were alive and without disease at time of last follow up (mean 38 months). All cases showed mucicarmine positive vacuolated/signet ring cells embedded in a myxoid stroma. Three cases showed at least focal p63 staining and two cases showed positivity for calponin. Membranous E-cadherin was retained in all cases. FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases. Based on the current series and the previously reported cases, it is evident that signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and thus as a whole more appropriately designated as 'secretory myoepithelial carcinoma.' They behave in a fairly indolent fashion and do not share the major molecular alterations seen in other signet ring and myoepithelial tumor types. © 2014 Springer Science+Business Media New York.
Abdul-Rasoul M.,Pediatric Endocrine Unit |
Al-Mahdi M.,Adan Hospital |
Al-Qattan H.,Adan Hospital |
Al-Tarkait N.,Sabah Hospital |
And 4 more authors.
Pediatric Diabetes | Year: 2010
Background: Diabetic ketoacidosis (DKA) has significant morbidity and mortality, and is common at diagnosis in children. Objective: Describe the frequency and severity of DKA at diagnosis of type 1 diabetes mellitus (T1DM) in children in Kuwait. Methods: Hospital records of 677 diabetic children less than 12 yr of age, diagnosed during the period of 2000-2006 were reviewed. DKA was defined as blood glucose > 11 mmol/L, pH < 7.3, and/or bicarbonate < 15 mmol/L with ketonuria. Results: Of all patients diagnosed with T1DM, 255 (37.7%) presented with DKA. The frequency of DKA was constant between 2000 and 2002 (42.7-41.5%), but decreased in the following years to 30.7% in 2006 (p < 0.005). The majority had either mild or moderate DKA (74.1%). Fifty-one (36.7%) of all children in the 0-4 yr had severe DKA compared to ten (2.9%) in the 5- to 8-yr-old group, and three (1.5%) in 9- to 12-yr-old patients (p < 0.0001). Moreover, 83% of children with severe DKA were in the 0-4 yr age group. One child (0.15%) died and twenty-seven (4%) needed intensive care unit (ICU) care. Conclusion: Our study provides recent data on Middle Eastern population, for whom data are sparse. Although it has significantly decreased, the frequency of DKA at presentation of T1DM in children in Kuwait is still high, secondary to the high prevalence of diabetes in the community. Young children, especially those less than 2 yr old remain at high risk. Increasing the general awareness of the public as well as of pediatricians to the disease may lead to early diagnosis before the development of acidosis. © 2009 John Wiley & Sons A/S.
Alfadhli S.,Kuwait University |
Almutawa Q.,Kuwait University |
Abbas J.M.K.,Sabah Hospital |
Doi S.A.R.,University of Queensland
Endocrine | Year: 2013
Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3′UTR (AT)n repeat] and the ICOS intron 4 (GT)n marker for their potential association with HT, and exploring the effect of the tested SNPs on the CTLA-4 isoform expression at the mRNA and protein levels. Total of 270 age-gender-ethnically matched subjects were genotyped by fluorescent-labelled restriction fragment length polymorphism, multiplex PCR, and fragment analysis. Sequencing was used to confirm the genotyping results. Expression of the full-length and soluble CTLA-4 mRNAs analysed using real-time PCR. Sera from subjects were screened for sCTLA-4 using ELISA. Tested subjects revealed ten alleles and sixteen genotypes of CTLA-4 3′UTR(AT)n. The 3′UTR(AT)n was significantly associated with HT: allele (AT)15 and genotype 15/15 were found to cause susceptibility to HT (P = 0.004, OR = 2.13, 95 % CI = 1.26-3.58 and P = 0.029, OR = 2.77, 95 % CI = 1.1-6.94, respectively), whereas allele (AT)6 and genotype 6/6 were found to be protective of HT (P = 0.00002, OR = 0.36, 95 % CI = 0.227-0.57 and P = 0.001, OR = 0.357, 95 % CI = 0.1980.64, respectively). SNP A49G and ICOS(GT)n revealed no significant association with HT (P > 0.05). The expression of sCTLA-4 was inversely proportional to the number of 3′UTR(AT)n repeats, with heterozygous and longer (AT)n repeats showing lower levels of sCTLA-4 mRNA than those with shorter alleles in HC and HT (P = 0.001 and P = 0.04, respectively). Significant increase in the serum level of sCTLA-4 was observed in HT patients compared with the HC (P = 0.0007). The novel finding in our study is that the CTLA-4 3′UTR(AT)n proven to be a key player in the pathogenesis of HT. © 2012 Springer Science+Business Media New York.
Eshra A.,Sabah Hospital
The Gulf journal of oncology | Year: 2010
Concomitant adenocarcinoma and non-Hodgkin's lymphoma, both located in the intestinal tract, are unusual. Collision tumors of the colon on the other hand are extremely rare neoplasms. A case of true collision tumor of a marginal zone lymphoma and a moderately differentiated adenocarcinoma of the ascending colon (hepatic flexure) is reported. Simultaneously, a third primary is identified as follicular lymphoma involving the terminal ileum. Correlation with clinical history, radiology investigations, endoscopic findings and histological examination of the resected specimen as well as the use of ancillary techniques such as immunohistochemistry are the most useful in making the correct diagnosis of a synchronous three primaries involving the small bowel and colon. Therefore, we present these three primary synchronous neoplasms involving two different parts of the gastrointestinal tract, with two of these three primaries colliding at one organ.