Neville J. De Young

Similarity of aberrant DNA methylation in Barrett's esophagus and esophageal adenocarcinoma

BackgroundBarretts esophagus (BE) is the metaplastic replacement of squamous with columnar epithelium in the esophagus, as a result of reflux. It is the major risk factor for the development of esophageal adenocarcinoma (EAC). Methylation of CpG dinucleotides of normally unmethylated genes is associated with silencing of their expression, and is common in EAC. This study was designed to determine at what stage, in the progression from BE to EAC, methylation of key genes occurs.ResultsWe examined nine genes (APC, CDKN2A, ID4, MGMT, RBP1, RUNX3, SFRP1, TIMP3, and TMEFF2), frequently methylated in multiple cancer types, in a panel of squamous (19 biopsies from patients without BE or EAC, 16 from patients with BE, 21 from patients with EAC), BE (40 metaplastic, seven high grade dysplastic) and 37 EAC tissues. The methylation frequency, the percentage of samples that had any extent of methylation, for each of the nine genes in the EAC (95%, 59%, 76%, 57%, 70%, 73%, 95%, 74% and 83% respectively) was significantly higher than in any of the squamous groups. The methylation frequency for each of the nine genes in the metaplastic BE (95%, 28%, 78%, 48%, 58%, 48%, 93%, 88% and 75% respectively) was significantly higher than in the squamous samples except for CDKN2A and RBP1. The methylation frequency did not differ between BE and EAC samples, except for CDKN2A and RUNX3 which were significantly higher in EAC. The methylation extent was an estimate of both the number of methylated alleles and the density of methylation on these alleles. This was significantly greater in EAC than in metaplastic BE for all genes except APC, MGMT and TIMP3. There was no significant difference in methylation extent for any gene between high grade dysplastic BE and EAC.ConclusionWe found significant methylation in metaplastic BE, which for seven of the nine genes studied did not differ in frequency from that found in EAC. This is also the first report of gene silencing by methylation of ID4 in BE or EAC. This study suggests that metaplastic BE is a highly abnormal tissue, more similar to cancer tissue than to normal epithelium.

Assessment of an electronic voting system within the tutorial setting: A randomised controlled trial [ISRCTN54535861]

BackgroundElectronic voting systems have been used in various educational settings with little measurement of the educational impact on students. The goal of this study was to measure the effects of the inclusion of an electronic voting system within a small group tutorial.MethodA prospective randomised controlled trial was run at the Royal Adelaide Hospital, a teaching hospital in Adelaide, Australia. 102 students in their first clinical year of medical school participated in the study where an electronic voting system was introduced as a teaching aid into a standard tutorial. Long-term retention of knowledge and understanding of the topics discussed in the tutorials was measured and student response to the introduction of the electronic voting system was assessed.ResultsStudents using the electronic voting system had improved long-term retention of understanding of material taught in the tutorial. Students had a positive response to the use of this teaching aid.ConclusionElectronic voting systems can provide a stimulating learning environment for students and in a small group tutorial may improve educational outcomes.

Decreased phagocytic capacity of autotransplanted splenic tissue

Background:  Asplenic patients have an increased risk of infections. Operations such as autotransplantation have been proposed to restore functional splenic tissue after splenectomy, but the protective value of this tissue is unclear. Immune responses such as production of antibody remain impaired in humans and animals even when such tissue is present, and clearance of particles from the blood is reported to be less efficient than by normal spleen tissue. The present study investigated the phagocytic capacity of cells in the regenerated tissue in vitro, free of the confounding effects of hepatic clearance.

Monocyte antibody-dependent cellular cytotoxicity in cancer patients

SummaryAntibody-dependent cellular cytotoxicity (ADCC) mediated by peripheral blood monocytes was determined in 120 patients who had gastrointestinal tract (GIT), lung and breast cancer, melanoma, or Hodgkins and non-Hodgkins lymphoma. Results were expressed in terms of maximum cytotoxicity and cytotoxicity at E : T=1 : 10 and were compared with the results obtained in 63 normal subjects. There was a significant decrease in maximal cytotoxicity for both the GIT cancer and the melanoma patient groups, but not for any of the other groups. These differences were not confirmed when results were expressed at low effector: target cell ratios, e.g., cytotoxicity at E : T=1 : 10. The relationship between monocyte ADCC and disease extent was examined in those groups with sufficient numbers. Monocyte ADCC was higher in patients with GIT cancer of limited extent than in patients with extensive GIT cancer and in the control group.

Immunoadsorbent purification of the carcinoembryonic antigen

Abstract Carcinoembryonic antigen (CEA), a carbohydrate-rich glycoprotein, has been purified from human tumour tissue by three methods: (i) the procedure of Krupey et al. (1972) involving extraction with 1 M perchloric acid; (ii) by immuno-affinity chromatography using anti-CEA antibodies coupled to Sepharose 4B; and (iii) by affinity chromatography on Concanavalin A-Sepharose. The immuno-affinity chromatography method was rapid and gave good yields of highly purified product, and the immuno-adsorbent could be used for many purification cycles. CEA is heterogeneous with respect to its binding to Concanavalin A-Sepharose. The major component was purified 27-fold using this affinity adsorbent, but the product still contained considerable amounts of impurities. CEAs purified from the same source by immuno-affinity chromatography and by the perchloric acid extraction method had similar mol. wts and electrophoretic mobility. However the immunoadsorbent-purified material had a higher ratio of carbohydrate to protein, 64.3% compared to 50.3%, implying that acid extraction resulted in partial degradation of the carbohydrate moiety. The two preparations were immunochemically similar but not identical.

Online, blended learning materials in psychiatry for medical students and trainees.

Thirty-three patients (66%) were exposed to SGAs (mean duration: 6.6 months). The mean BMI was 26.95 kg/m2. This compares similarly to that of Patel and colleagues,4 who reported this figure as 27.6 kg/m2. The prevalence of being overweight (BMI = 85th–95th percentile) or obesity (BMI > 95th percentile) was 46.6%. Previous studies have reported figures between 31% and 68%.4–6 Ten per cent met a full diagnosis of Cook’s positive MS, while 40% satisfied at least one of the criteria. Of the obese/overweight patients on SGAs, 42.9% had elevated triglyceride levels. Rates in other studies4 were 51%. Similarly, 71.4% of patients on SGAs who were obese/overweight were ‘at risk’. Thirty-six per cent had 1–2 of Cook’s criteria, while 48% had at least one abnormality as defined by Correll’s criteria. The most common metabolic abnormality was elevated triglycerides. Psychological distress was reported in 40%. The symptoms included low mood, crying, social isolation, low self-esteem, poor body image, sleep problems, self-blame, guilt, anger and irritability.