Brazilian consensus on gastroesophageal reflux disease: proposals for assessment, classification, and management

The Brazilian Consensus on Gastroesophageal Reflux Disease considers gastroesophageal reflux disease to be a chronic disorder related to the retrograde flow of gastroduodenal contents into the esophagus and/or adjacent organs, resulting in a variable spectrum of symptoms, with or without tissue damage. Considering the limitations of classifications currently in use, a new classification is proposed that combines three criteria-clinical, endoscopic, and pH-metric-providing a comprehensive and more complete characterization of the disease. The diagnosis begins with the presence of heartburn, acid regurgitation, and alarm manifestations (dysphagia, odynophagia, weight loss, GI bleeding, nausea and/or vomiting, and family history of cancer). Also, atypical esophageal, pulmonary, otorhinolaryngological, and oral symptoms may occur. Endoscopy is the first approach, particularly in patients over 40 yr of age and in those with alarm symptoms. Other exams are considered in particular cases, such as contrast radiological examination, scyntigraphy, manometry, and prolonged pH measurement. The clinical treatment encompasses behavioral modifications in lifestyle and pharmacological measures. Proton pump inhibitors in manufacturers' recommended doses are indicated, with doubling of the dose in more severe cases of esophagitis. The minimum time of administration is 6 wk. Patients who do not respond to medical treatment, including those with atypical manifestations, should be considered for surgical treatment. Of the complications of gastroesophageal reflux disease, Barrett's esophagus presents a potential development of adenocarcinoma; biopsies should be performed, independent of Barrett's esophagus extent or location. In this regard the designation "short Barrett's" is not important in terms of management and prognosis.     

Altered cardia epithelial cell kinetics induced by Helicobacter pylori infection and gastro-oesophageal reflux disease: possible malignant potential?

BACKGROUND: The incidence of adenocarcinoma of the proximal stomach (cardia) is increasing. The pathophysiological processes underlying this trend are unclear. Normal cell turnover depends on cell proliferation being in balance with programmed cell death or apoptosis. It has been well documented that excessive proliferation potentiates the effects of any carcinogen that targets DNA. It is therefore accepted that excessive proliferation is a risk factor for subsequent neoplasia development. AIMS: To compare apoptosis and proliferation in normal cardia tissue, carditis, and cardia intestinal metaplasia, and to determine the effect of Helicobacter pylori infection and gastro-oesophageal reflux disease. METHODS: Biopsies from the cardia were obtained from consecutive dyspeptic patients and asymptomatic controls at the time of gastroscopy. Samples were assessed histologically and classified as normal, carditis, or cardia tissue with intestinal metaplasia. All samples were then examined, employing immunohistochemical techniques, for the presence of proliferating and apoptotic cells. RESULTS: A total of 76 histological specimens were examined. There was a statistical significant difference in the proliferation index between controls and both carditis and cardia intestinal metaplasia, and also between carditis and cardia intestinal metaplasia. In contrast, there was a significant increase in the apoptotic index for carditis compared with controls, while that of intestinal metaplasia did not differ from controls. As a result, comparison of the apoptotic/proliferation ratios for each group revealed that, for both carditis and cardia intestinal metaplasia, the apoptotic index/proliferation index ratio is reduced significantly compared with controls, but as a result of different mechanisms. CONCLUSION: This study demonstrates that individuals with carditis and cardia intestinal metaplasia have alterations in epithelial cell kinetics. In particular, it shows that there is a persistent imbalance between proliferation and apoptosis, which may represent malignant potential.     

P450c17 deficiency in Brazilian patients: biochemical diagnosis through progesterone levels confirmed by CYP17 genotyping

P450c17 deficiency is an autosomal recessive disorder and a rare cause of congenital adrenal hyperplasia characterized by hypertension, hypokalemia, and impaired production of sex hormones. We performed a clinical, hormonal, and molecular study of 11 patients from 6 Brazilian families with the combined 17alpha-hydroxylase/17,20-lyase deficiency phenotype. All patients had elevated basal serum levels of progesterone (1.8-38 ng/ml; 0.57-12 pmol/liter) and suppressed plasma renin activity. CYP17 genotyping identified 5 missense mutations. The compound heterozygous mutation R362C/W406R was found in 1 family, whereas the homozygous mutations R96W, Y329D, and P428L were seen in the other 5 families. The R96W mutation has been described as the cause of p450c17 deficiency in Caucasian patients. The other mutations were not found in 50 normal subjects screened by allele-specific oligonucleotide hybridization (Y329D, R362C, and W406R) or digestion with HphI (P428L) and were recently found in other Brazilian patients. Therefore, we elucidated the genotype of 11 individuals with p450c17 deficiency and concluded that basal progesterone measurement is a useful marker of p450c17 deficiency and that its use should reduce the misdiagnosis of this deficiency in patients presenting with male pseudohermaphroditism, primary or secondary amenorrhea, and mineralocorticoid excess syndrome.     

Clinical,biochemical and immunological characteristic of diabetes type I,LADA, diabetes type II,and MODY patients

Right classification of diabetes is important clinical issue. The aim of present study was to compare clinical, biochemical and immunological features, to analyze their practical use and to establish new decision tree which make the distinction between diabetes type 1, LADA, diabetes type 2 and MODY. We studied 97 not obese (mean BMI 26.3 +/- 4.9 kg/m2) patients aged 14 to 70 years, mean age 43 +/- 11.7 years, 53 women, 44 men. Mean duration of diabetes--2.3 +/- 4.3 years. We measured basal and stimulated C-peptide (6 minutes after 1 mg i.v. glucagon) (ELISA) and antibodies titers to glutamic acid decarboxylase--antiGAD65, tyrosine phosphatase-like molecule--IA2 and insulin--IAA (RIA). Autoimmune diabetes (LADA, type 1) was diagnosed with presence of one or more islet antigen antibodies. The highest frequencies had anti-GAD antibodies 33/97 (34%). The most complicated was to sort out group of patients with LADA. Comparison between this group and patients with diabetes type 2 have shown that BMI, co-existence of autoimmune disease, autoimmune markers and basal and stimulated C-peptide level measured at entry for the classification were useful in differentiation. Moreover we observed significantly lower C-peptide basal, stimulated and over basal level in group with MODY diabetes in comparison to diabetes type 2 patients. In the studied group were 5 patients with diabetes type 2 and obesity, in relatively young age. At the end there was one case of ADM (atypical diabetes mellitus). Clinical criteria for the classification of diabetes not always correlated with diagnosis. Autoimmune markers, basal and stimulated C-peptide were useful specially in differentiation between LADA and diabetes type 2 or diabetes type 1. Autoimmune diabetes co-existe with autoimmune disease. Proposed diagnostic scheme take for consideration presence of autoantibodies as well as C-peptide criteria.     

Safety and efficacy of therapy with botulinum toxin in obesity: a pilot study

Background Botulin toxin (BTX) has been proposed as a potential obesity treatment.Methods In a pilot study, the short-term efficacy and safety of BTX was assessed in eight subjects (four men, four women; median age, 46 years; range, 35–57 years) with severe obesity (median body mass index [BMI], 47.1 kg/m²; range 38.2–56.7 kg/m²) and multiple dietary treatment failures. In a single endoscopic session, 500 UI of BTX-A was injected in the gastric antral region.Results No clinically significant side effects were observed. In all patients, despite their not being on a specific diet, a reduction of body weight was observed at 1 month (median baseline weight, 124.4 kg vs 121.8 kg at 1 month; P < 0.05). Two treatment-unrelated dropouts were observed. At 4 months, three of the six patients had a further weight loss. The treatment effect was apparently independent of changes in hunger or satiety, or of changes in fasting and postprandial plasma ghrelin and serum leptin, thus suggesting a different pharmacological mechanism.Conclusions BTX-A treatment appears to be safe and well tolerated by obese patients, while its short-term efficacy varied widely.