Global DNA hypomethylation occurs in the early stages of intestinal type gastric carcinoma.

BACKGROUND: Global DNA hypomethylation has been found in the premalignant stages of some neoplasms and has been implicated as an important factor for tumour progression. AIMS: The aim of this study was to evaluate whether DNA hypomethylation occurs during the process of gastric carcinogenesis. METHODS: Gastric specimens were obtained from 49 patients and histologically classified as: normal 10, superficial gastritis 14, chronic atrophic gastritis with intestinal metaplasia 15, and intestinal type of gastric carcinoma 10. Global DNA methylation was assessed by incubating DNA with (3H)-S-adenosylmethionine and Sss1 methylase. A higher incorporation of (3H) methyl groups reflects a lower degree of intrinsic methylation. RESULTS: A graduated increase in (3H) methyl group incorporation into DNA was found over the range extending from normal gastric mucosa, to superficial gastritis and to chronic atrophic gastritis (136,556 (24,085) v 235,725 (38,636) v 400,998 (26,747 dpm/micrograms/DNA respectively; p = 0.0002). No further increase was found in specimens from patients with carcinoma. No differences were found between extent of DNA methylation in neoplastic or non-neoplastic mucosa from patients with gastric carcinoma. Hypomethylation of DNA increased substantially with severe atrophy (p = 0.01) or with type III intestinal metaplasia (p = 0.15). CONCLUSIONS: Global DNA hypomethylation occurs in the early stages of gastric carcinogenesis, and it may be a novel biomarker of gastric neoplasia, useful in monitoring the response to chemopreventive agents.     

Tissue Doppler imaging and long axis left ventricular function: hypertrophic cardiomyopathy versus athlete's heart.

BACKGROUND: The different diagnosis between hypertrophic cardiomyopathy and athlete's heart has important clinical implications. The assessment of long axis left ventricular function with tissue Doppler imaging in hypertrophic cardiomyopathy (showing systolic and diastolic dysfunction with heterogeneity and asynchrony), may be useful in the differentiation of these situations. AIM: To study, with tissue Doppler imaging, long axis left ventricular function in a population of athletes (rowers) and to compare it with a population of non-obstructive hypertrophic cardiomyopathy patients. METHODS: In 24 patients with non-obstructive hypertrophic cardiomyopathy and in 20 competitive rowers with similar age, blood pressure and heart rate, we analyzed mitral annulus motion with pulsed tissue Doppler imaging in the 4 sides of the annulus (septal, lateral, inferior, anterior), in apical views. In each wave (systolic, rapid filling and atrial contraction) we measured velocities, time intervals and velocity-time integrals, and calculated heterogeneity and asynchrony indices. Data were compared between the groups, between the different sides in each group ("parallel analysis") and with conventional indices of global function. RESULTS: Hypertrophic cardiomyopathy patients showed: systolic function: lower velocities and integrals, shorter ejection time and shorter systolic time. These abnormalities occurred even in annular sites contiguous to walls without hypertrophy. DIASTOLIC FUNCTION: Much lower rapid filling velocities and integrals, lower atrial contraction velocities and integrals, lower e/a, longer isovolumic relaxation time and time to peak rapid filling wave. These abnormalities occurred even in annular sites adjacent to walls without hypertrophy. In the athletes group, the e/a ratio was never < 1, in any annular site. In hypertrophic cardiomyopathy patients this ratio was < 1 in 27% of the sites. CONCLUSIONS: 1--Systolic and diastolic long axis left ventricular function is different in hypertrophic cardiomyopathy and in athletes, in all mitral annulus sides. 2--The presence of these abnormalities in annular sites contiguous to walls without hypertrophy suggests that this technique may be useful in the differential diagnosis between these groups, particularly in the "gray zone" of Maron.     

Physiological concentrations of melatonin inhibit the nitridergic pathway in the Syrian hamster retina

In the present work, the effect of melatonin on the hamster retinal nitridergic pathway was examined. When the retinas were incubated in the presence of low concentrations (1 pM-10 nM) of melatonin for 15 min, a significant decrease of nitric oxide synthase (NOS) activity was observed. However, when crude retinal homogenates were preincubated with melatonin for 15 min, no changes in NOS activity were detected, despite the fact that under the same conditions trifluoperazine, a calmodulin inhibitor, significantly decreased enzymatic activity. Kinetic analysis showed that melatonin decreased the V(max) of retinal NOS without changes in the K(m). On the other hand, low concentrations (100 pM) of melatonin significantly reduced retinal L-arginine influx. A decrease in the V(max) of L-arginine uptake was observed in the presence of melatonin, whereas the K(m) remained unchanged. Melatonin significantly inhibited the accumulation of cyclic guanosine monophosphate (cGMP) levels induced by both L-arginine and sodium nitroprusside (SNP). In summary, the present results indicate that melatonin could be a potent inhibitor of the retinal nitridergic pathway.     

Should we try to determine the specific cause of cardiac tamponade?

INTRODUCTION: The causes of cardiac tamponade vary and it has been suggested that underlying causes should be sought in all cases. The purpose of this study was to determine the causes of cardiac tamponade in our environment, distinguishing between specific and idiopathic causes, and analyzing the proportion and causes in the subgroup of patients with relapsing tamponade. PATIENTS AND METHOD: We retrospectively studied all patients who underwent therapeutic pericardiocentesis between 1985 and 2001. The clinical and radiographic features and macroscopic characteristics of the pericardial fluid were analyzed. The final diagnosis in each patient was based on the clinical history, follow-up, pericardial fluid cytology, and pericardial biopsy, if available. RESULTS: Ninety-six patients were included (52 men/44 women), mean age 56.1 16.1 years. The cause of pericardial effusion was neoplasm in 50 patients (52.1%), 14 idiopathic pericarditis (14.6%), 12 renal failure (12.5%), 7 iatrogenic cases (7.3%), 4 mechanical tamponades (4.2%), 2 tuberculosis (2.1%), and 7 other causes (7.3%). Thirty-five patients had relapsing tamponade; only 2 of them had idiopathic pericarditis (5.7%). We found no significant differences in age, development time, extracted volume or fluid features between tamponade of specific or idiopathic origin. CONCLUSIONS: Most of the cardiac tamponades in our series had a specific cause. This made it necessary to identify a specific underlying cause in each case, especially in relapsing effusions. However, we did not find any variable suggestive of the cause of the disease.     

Revisiting serum thyroglobulin in the follow-up of patients with differentiated thyroid carcinoma

This study analyzed serum thyroglobulin (Tg) during hypothyroidism in 207 patients with differentiated thyroid carcinoma treated with total thyroidectomy and radioiodine ablation and undetectable anti-Tg antibodies. Disease staging was defined by clinical examination, stimulated Tg, pre- and post-ablative radioiodine scanning, and other imaging methods (X-Ray, US, CT and MIBI-scan). The average interval from initial therapy was 2.3 years. 153 patients (74%) had no evident disease, 34 (16.4%) presented neck/mediastinal disease, and 20 (9.6%) had distant metastases (Mt). The best cut-off for Tg was 1 ng/ml, showing 100% sensitivity for distant Mt and 88.2% for local recurrence or lymph node Mt, and 88.8% specificity for any Mt and 74.8% for distant Mt. In patients with Tg <1 ng/ml, 2.8% showed cervical lymph nodes Mt. Cervical or mediastinal disease were 26% of cases with Tg between 1 and 5 ng/ml. Tg from 5 to 10 ng/ml was associated to distant Mt in 14.2% of the cases and others showed lymph nodes Mt. In patients with Tg >10 ng/ml, 51.3% presented distant Mt. We suggest the need for neck US even in cases with Tg <1 ng/ml. In addition, patients with Tg levels <5 ng/ml should be investigated by neck US and mediastinal CT only, and empirical therapy should be limited to patients with a minimum Tg level >5 ng/ml.     

Pinealectomy exaggerates and melatonin treatment suppresses neuroma formation of transected sciatic nerve in rats: gross morphological, histological and stereological analysis

At present, an intensive effort for prevention of neuroma formation following peripheral nerve section continues. It has been recently suggested that surgical pinealectomy (Px) induces elevation of the collagen content in the granulation tissue of a wound, while melatonin application after Px suppresses elevation of the collagen accumulation in the tissue. The aim of the present study was to assess whether melatonin had the ability to suppress collagen production and neuroma formation following peripheral nerve transection. A total of 40 male rats (four groups of 10) were left intact (intact controls) or sham operated (sham group), were Px, or were Px and given melatonin (Px + melatonin group). All animals underwent a surgical intervention consisting of right sciatic nerve neurectomy. After 4 wk, the animals were killed following intracardiac perfusion. Gross morphology of neuroma formation in the proximal nerve segment was examined and proximal neuroma evaluated. Macroscopic and microscopic findings revealed that Px caused a proliferation of connective tissue and large neuroma formation at the proximal ends of transected nerves. Stereological analysis showed that there was a statistically significant reduction in connective tissue content of the same region in Px animals treated with melatonin (P < 0.005). The results achieved in a rodent model of sciatic nerve neuroma formation showed that there was a positive correlation between macroscopic and microscopic observations, and that melatonin enhanced axonal regeneration presumably due to its inhibitory effect on neuroma formation.     

Rendimiento diagnóstico de la secuenciación de genes de hipercolesterolemia familiar en sujetos con hipercolesterolemia primaria

Introduction and objectivesOur objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations.MethodsUnrelated individuals aged ≥ 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology.ResultsOf 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011).ConclusionsOur results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test.