Detection and reporting of RB1 promoter hypermethylation in diagnostic screening

Background: RB1 gene screening aids clinical management and genetic counselling in retinoblastoma families. Here we present epigenetic changes identified during routine molecular RB1 screening of tumor and blood samples. Complications in interpreting RB1 methylation are discussed.

Materials and Methods: Screening for RB1 promoter hypermethylation was carried out by Methylation Specific PCR (MS-PCR) after bisulphite modification of DNA. The cohort consisted of 315 tumors, and 204 blood samples, from 497 retinoblastoma patients (22 patients had both blood and tumor screened).

Results: 11.4% of retinoblastoma tumors had promoter hypermethylation. It was not routinely detected in blood samples, or in tumors with two other oncogenic RB1 changes. One blood sample had promoter hypermethylation due to an X;13 translocation. One tumor had low level methylation as well as two other oncogenic changes. Histopathological analysis of a small subset of age-matched tumors was similar regardless of promoter hypermethylation status.

Conclusions: Promoter hypermethylation was detected in 11.4% of the retinoblastoma tumors and should be tested for in routine RB1 screening programmes. Constitutional samples are not expected to display RB1 hypermethylation. In a small proportion of cases it may not be possible to use this somatic change in patient management.     

Circulating leptin and body composition in chronic obstructive pulmonary disease

Nutritional depletion and weight loss are two features of chronic obstructive pulmonary disease (COPD), and the association between low body mass index (BMI) and poor prognosis in patients with COPD is a common clinical observation. Mechanisms of weight loss are still unclear in COPD. Excessive energy expenditure partly due to increased work of breathing was shown, but other mechanisms have been searched for. Leptin is a hormone secreted by adipocytes that plays an important role in energy homeostasis and regulates body weight through control of appetite and energy expenditure. The aim of this study was to evaluate the association of circulating leptin levels and measures of body composition in COPD patients. Thirty male COPD outpatients (mean age 66.3 +/- 8.4) and 20 controls (mean age 65.9 +/- 10.8) were included in the study. After standard spirometry and body composition measurements, serum leptin concentration was measured by ELISA assay. COPD patients were grouped according to BMI. Mean BMI was 19.01 +/- 2.26 kg/m2 in group 1 (COPD patients with low BMI), 26.85 +/- 4.51 in group 2 COPD (COPD patients with normal/high BMI) and 27.64 +/- 2.75 kg/m2 in healthy controls (group 3). Mean serum leptin concentration was 1.41 +/- 1.86 ng/ml in group 1, 2.60 +/- 1.38 ng/ml in group 2 and 2.82 +/- 1.46 ng/ml in group 3 (p = 0.002). Leptin correlated to not only BMI but also body weight, waist circumference, triceps and biceps skinfold thickness and body fat percent (p < 0.05 for all). Results of this study suggest that the cause of weight loss is not increased circulating leptin in COPD. Instead, leptin remains regulated in COPD and further decreased in patients with low BMI, probably as a compensatory mechanism to preserve body fat content, which should be evaluated in further studies.     

Circulating ghrelin levels in obese women: a possible association with hypertension

OBJECTIVE: The orexigenic hormone ghrelin induces weight gain by stimulating food intake. Ghrelin has been shown to modulate sympathetic activity, to exert vasodilative effects and to counterreact with leptin on both food intake and blood pressure. Of these two hormones, ghrelin levels are decreased in obesity, whereas leptin levels are increased. In this cross-sectional study, differences in serum ghrelin and leptin levels were examined in normotensive and hypertensive obese women. MATERIAL AND METHODS: Sixty-one normotensive and hypertensive women were classified according to the body mass indices as follows: (a) 18 healthy subjects with BMI 21.5-27.5 kg/m(2); (b) 22 normotensive subjects with BMI 30-47 kg/m(2); (c) 21 hypertensive obese subjects (BMI 30-48 kg/m(2)) with systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg. Anthropometric measurements including height, weight, BMI, waist and hip circumferences and blood pressure were recorded. The levels of ghrelin and leptin were determined in sera using the commercial ELISA kits. RESULTS: In normotensive obese subjects, ghrelin levels were significantly lower than in controls (0.21+/-0.13 vs 0.60+/-0.3 ng/mL), whereas hypertensive obese women had elevated ghrelin levels (0.64+/-0.36 ng/mL). Ghrelin concentration was decreased despite the presence of hypertension in the patients who had BMIs above 35 kg/m(2). Leptin levels were significantly higher in both normotensive and hypertensive obese groups (19.54+/-11.19 and 21.61+/-12.7 ng/mL, respectively) than in controls (7.61+/-3.3 ng/mL), and were not affected by the presence of hypertension in obese subjects. CONCLUSION: Ghrelin was positively associated with hypertension in obese women and this association was inversely influenced by the increase of BMI.     

Editorial Commentary: Fracture Risk After Arthroscopic Osteochondroplasty for Femoroacetabular Impingement—How Can We Become Better?

There is an increased risk of fracture following osteochondroplasty at the femoral head–neck junction for cam-type femoroacetabular impingement. The amount of safe resection has previously been investigated through several biomechanical models, including composite bone, cadaver, animal, and finite element models. Translation of ex vivo results regarding safe resection to an arthroscopic procedure on an actual patient remains a research and clinical challenge.     

Upper-extremity deep vein thrombosis and downhill esophageal varices caused by long-term pacemaker implantation

Upper-extremity deep vein thrombosis is common after pacemaker or cardioverter-defibrillator implantation. Only 1% to 3% of patients with upper-extremity deep vein thrombosis become symptomatic. Downhill esophageal varices develop in the upper third of the esophagus as a result of the obstruction of the superior vena cava. Herein, we report the case of a 54-year-old man--a recipient of multiple implanted cardiac pacemakers--who presented with bilateral upper-extremity deep vein thrombosis. This severely symptomatic condition was complicated by very rare and life-threatening downhill varices of the upper esophagus, but without bleeding. To the best of our knowledge, this is the 1st report of this array of conditions.     

Prevalence patterns of gastric cancers in Turkey: model of a developing country with high occurrence of Helicobacter pylori

AIM: In developed countries, there has been a recent increase in the prevalence of adenocarcinoma of the esophagus and cardia, along with a decrease in distal gastric cancers. Little is known regarding the prevalence of these diseases in developing countries. The aim of the present study was to evaluate changes in the prevalence of gastric adenocarcinomas in Turkey as a function of anatomic location. METHODS: Data were retrospectively collected from 16 centers from January 1990 to December 2000. Owing to the exclusion criteria, a total of 4065 cases of tumors of the stomach and distal esophagus were included. Tumors localized to the body, the antrum and pyloric channel were considered distal cancers. Helicobacter pylori (H. pylori) was also detected. RESULTS: Patients' mean age was 60.7 +/- 9 years, with a male : female ratio of 68:32. The ratio of distal/proximal adenocarcinoma was 2:1 for the western part of Turkey and 3:8 for the eastern part of the country (P < 0.0001), and this did not change during the 11 years. H. pylori was detected significantly less in the west compared to the east for distal tumors (65.7 vs 38.7%, respectively, P = 0.02). CONCLUSION: In Turkey, a developing country with a high H. pylori prevalence, contrary to the state of developed countries, the ratio of distal versus proximal gastric adenocarcinomas has not changed. Geographical distribution should be taken into the account in projecting the changing patterns of gastric cancers.