Genome-wide scan reveals genomic regions and candidate genes underlying direct and maternal effects of preweaning calf mortality in Nellore cattle.

We conducted analysis to estimate genetic parameters and to identify genomic regions and candidate genes affecting direct and maternal effects of preweaning calf mortality (PWM) in Nellore cattle. Phenotypic records of 67,196 animals, and 8443 genotypes for 410,936 SNPs were used. Analysis were performed through the weighted single-step GBLUP approach and considering a threshold animal model via Bayesian Inference. Direct and maternal heritability estimates were of 0.2143 ± 0.0348 and 0.0137 ± 0.0066, respectively. The top 10 genomic regions accounted for 13.61 and 14.23% of the direct and maternal additive genetic variances and harbored a total of 63 and 91 positional candidate genes, respectively. Two overlapping regions on BTA2 were identified for both direct and maternal effects. Candidate genes are involved in biological mechanisms i.e. embryogenesis, immune response, feto-maternal communication, circadian rhythm, hormone alterations, myometrium adaptation, and milk secretion, which are critical for the successful calf growth and survival during preweaning period.

Genome-wide association study identified genomic regions and putative candidate genes affecting meat color traits in Nellore cattle.

Single and multiple-trait GWAS were conducted to detect genomic regions and candidate genes associated with meat color traits (L*, lightness; a*, redness; b*, yellowness) in Nellore cattle. Phenotypic records of 5000 animals, and 3794 genotypes for 614,274 SNPs were used. The BLUPF90 family programs were used through single step GWAS approach. The top 10 genomic regions from single-trait GWAS explained 13.64%, 15.12% and 13% of genetic variance of L*, a* and b*, which harbored 129, 70, and 84 candidate genes, respectively. Regarding multiple-trait GWAS, the top 10 SNP windows explained 17.46%, 18.98% and 13.74% of genetic variance of L*, a* and b*, and harbored 124, 86, and 82 candidate genes, respectively. Pleiotropic effects were evidenced by the overlapping regions detected on BTA 15 and 26 associated with L* and a* (genetic correlation of -0.53), and on BTA 18 associated with a* and b* (genetic correlation of 0.60). Similar genomic regions located on BTA 2, 5, 6, and 18 were detected through single and multi-trait GWAS. Overlapped regions harbored a total of 30 functional candidate genes involved in mitochondrial activity, structural integrity of muscles, lipid oxidation, anaerobic metabolism, and muscular pH.

Genomic reaction norm models exploiting genotype × environment interaction on sexual precocity indicator traits in Nellore cattle.

Brazilian beef cattle are raised predominantly on pasture in a wide range of environments. In this scenario, genotype by environment (G×E) interaction is an important source of phenotypic variation in the reproductive traits. Hence, the evaluation of G×E interactions for heifer's early pregnancy (HP) and scrotal circumference (SC) traits in Nellore cattle, belonging to three breeding programs, was carried out to determine the animal's sensitivity to the environmental conditions (EC). The dataset consisted of 85 874 records for HP and 151 553 records for SC, from which 1800 heifers and 3343 young bulls were genotyped with the BovineHD BeadChip. Genotypic information for 826 sires was also used in the analyses. EC levels were based on the contemporary group solutions for yearling body weight. Linear reaction norm models (RNM), using pedigree information (RNM_A) or pedigree and genomic information (RNM_H), were used to infer G×E interactions. Two validation schemes were used to assess the predictive ability, with the following training populations: (a) forward scheme-dataset was split based on year of birth from 2008 for HP and from 2011 for SC; and (b) environment-specific scheme-low EC (-3.0 and -1.5) and high EC (1.5 and 3.0). The inclusion of the H matrix in RNM increased the genetic variance of the intercept and slope by 18.55 and 23.00% on average respectively, and provided genetic parameter estimates that were more accurate than those considering pedigree only. The same trend was observed for heritability estimates, which were 0.28-0.56 for SC and 0.26-0.49 for HP, using RNM_H, and 0.26-0.52 for SC and 0.22-0.45 for HP, using RNM_A. The lowest correlation observed between unfavorable (-3.0) and favorable (3.0) EC levels were 0.30 for HP and -0.12 for SC, indicating the presence of G×E interaction. The G×E interaction effect implied differences in animals' genetic merit and re-ranking of animals on different environmental conditions. SNP marker-environment interaction was detected for Nellore sexual precocity indicator traits with changes in effect and variance across EC levels. The RNM_H captured G×E interaction effects better than RNM_A and improved the predictive ability by around 14.04% for SC and 21.31% for HP. Using the forward scheme increased the overall predictive ability for SC (20.55%) and HP (11.06%) compared with the environment-specific scheme. The results suggest that the inclusion of genomic information combined with the pedigree to assess the G×E interaction leads to more accurate variance components and genetic parameter estimates.

Genome scan for postmortem carcass traits in Nellore cattle.

Carcass traits measured after slaughter are economically relevant traits in beef cattle. In general, the slaughter house payment system is based on HCW. Ribeye area (REA) is associated with the amount of the meat in the carcass, and a minimum of backfat thickness (BFT) is necessary to protect the carcass during cooling. The aim of this study was to identify potential genomic regions harboring candidate genes affecting those traits in Nellore cattle. The data set used in the present study consisted of 1,756 Nellore males with phenotype records. A subset of 1,604 animals had both genotypic and phenotypic information. Genotypes were generated based on a panel with 777,962 SNPs from the Illumina Bovine HD chip. The SNP effects were calculated based on the genomic breeding values obtained by using the single-step GBLUP approach and a genomic matrix re-weighting procedure. The proportion of the variance explained by moving windows of 100 consecutive SNPs was used to assess potential genomic regions harboring genes with major effects on each trait. The top 10 non-overlapping SNP-windows explained 8.72%, 11.38%, and 9.31% of the genetic variance for REA, BFT, and HCW, respectively. These windows are located on chromosomes 5, 7, 8, 10, 12, 20, and 29 for REA; chromosomes 6, 8, 10, 13, 16, 17, 18, and 24 for BFT; and chromosomes 4, 6, 7, 8, 14, 16, 17, and 21 for HCW. For REA, there were identified genes ( and ) involved in the cell cycle biological process which affects many aspects of animal growth and development. The and genes, both from AA transporter family, was also associated with REA. The AA transporters are essential for cell growth and proliferation, acting as carriers of tissue nutrient supplies. Various genes identified for BFT (, , , , , and ) have been associated with lipid metabolism in different mammal species. One of the most promising genes identified for HCW was the . There is evidence, in the literature, that this gene is located in putative QTL affecting carcass weight in beef cattle. Our results showed several genomic regions containing plausible candidate genes that may be associated with carcass traits in Nellore cattle. Besides contributing to a better understanding of the genetic control of carcass traits, the identified genes can also be helpful for further functional genomic studies.

Accuracies of genomic prediction of feed efficiency traits using different prediction and validation methods in an experimental Nelore cattle population.

Animal feeding is the most important economic component of beef production systems. Selection for feed efficiency has not been effective mainly due to difficult and high costs to obtain the phenotypes. The application of genomic selection using SNP can decrease the cost of animal evaluation as well as the generation interval. The objective of this study was to compare methods for genomic evaluation of feed efficiency traits using different cross-validation layouts in an experimental beef cattle population genotyped for a high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA). After quality control, a total of 437,197 SNP genotypes were available for 761 Nelore animals from the Institute of Animal Science, Sertãozinho, São Paulo, Brazil. The studied traits were residual feed intake, feed conversion ratio, ADG, and DMI. Methods of analysis were traditional BLUP, single-step genomic BLUP (ssGBLUP), genomic BLUP (GBLUP), and a Bayesian regression method (BayesCπ). Direct genomic values (DGV) from the last 2 methods were compared directly or in an index that combines DGV with parent average. Three cross-validation approaches were used to validate the models: 1) YOUNG, in which the partition into training and testing sets was based on year of birth and testing animals were born after 2010; 2) UNREL, in which the data set was split into 3 less related subsets and the validation was done in each subset a time; and 3) RANDOM, in which the data set was randomly divided into 4 subsets (considering the contemporary groups) and the validation was done in each subset at a time. On average, the RANDOM design provided the most accurate predictions. Average accuracies ranged from 0.10 to 0.58 using BLUP, from 0.09 to 0.48 using GBLUP, from 0.06 to 0.49 using BayesCπ, and from 0.22 to 0.49 using ssGBLUP. The most accurate and consistent predictions were obtained using ssGBLUP for all analyzed traits. The ssGBLUP seems to be more suitable to obtain genomic predictions for feed efficiency traits on an experimental population of genotyped animals.

Genetic parameter estimates for carcass traits and visual scores including or not genomic information.

The objective of this study was to determine whether visual scores used as selection criteria in Nellore breeding programs are effective indicators of carcass traits measured after slaughter. Additionally, this study evaluated the effect of different structures of the relationship matrix ( and ) on the estimation of genetic parameters and on the prediction accuracy of breeding values. There were 13,524 animals for visual scores of conformation (CS), finishing precocity (FP), and muscling (MS) and 1,753, 1,747, and 1,564 for LM area (LMA), backfat thickness (BF), and HCW, respectively. Of these, 1,566 animals were genotyped using a high-density panel containing 777,962 SNP. Six analyses were performed using multitrait animal models, each including the 3 visual scores and 1 carcass trait. For the visual scores, the model included direct additive genetic and residual random effects and the fixed effects of contemporary group (defined by year of birth, management group at yearling, and farm) and the linear effect of age of animal at yearling. The same model was used for the carcass traits, replacing the effect of age of animal at yearling with the linear effect of age of animal at slaughter. The variance and covariance components were estimated by the REML method in analyses using the numerator relationship matrix () or combining the genomic and the numerator relationship matrices (). The heritability estimates for the visual scores obtained with the 2 methods were similar and of moderate magnitude (0.23-0.34), indicating that these traits should response to direct selection. The heritabilities for LMA, BF, and HCW were 0.13, 0.07, and 0.17, respectively, using matrix and 0.29, 0.16, and 0.23, respectively, using matrix . The genetic correlations between the visual scores and carcass traits were positive, and higher correlations were generally obtained when matrix was used. Considering the difficulties and cost of measuring carcass traits postmortem, visual scores of CS, FP, and MS could be used as selection criteria to improve HCW, BF, and LMA. The use of genomic information permitted the detection of greater additive genetic variability for LMA and BF. For HCW, the high magnitude of the genetic correlations with visual scores was probably sufficient to recover genetic variability. The methods provided similar breeding value accuracies, especially for the visual scores.

Genetic association of growth traits with carcass and meat traits in Nellore cattle.

The aim of this study was to estimate genetic and phenotypic associations of growth traits with carcass and meat traits in Nellore cattle. Data from male and female animals were used for weaning weight (WW; N = 241,416), yearling weight (YW, N = 126,596), weight gain from weaning to yearling (GWY, N = 78,687), and yearling hip height (YHH, N = 90,720), respectively; 877 male animals were used for hot carcass weight (HCW) and 884 for longissimus muscle area (LMA), backfat thickness (BT), marbling score (MS), and shear force (SF). The variance components were estimated by the restricted maximum likelihood method using three-trait animal models that included WW. The model for WW included direct and maternal additive genetic, maternal permanent environmental, and residual effects as random effects; contemporary group as fixed effects; and age of dam at calving and age of animal as covariates (linear and quadratic effects). For the other traits, maternal effects and the effect of age of dam at calving were excluded from the model. Heritability ranged from 0.10 ± 0.12 (LMA) to 0.44 ± 0.007 (YW). Genetic correlations ranged from -0.40 ± 0.38 (WW x LMA) to 0.55 ± 0.10 (HCW x YW). Growth, carcass, and meat traits have sufficient genetic variability to be included as selection criteria in animal breeding programs.

Chemical composition and dry matter digestibility of sugar cane oxide treated with calcium / Composição química e digestibilidade da matéria seca da cana-de-açúcar tratada com óxido de cálcio

The aim of this study was to identify the most adequate level of calcium oxide (CaO) in the treatment of sugar cane by evaluating the chemical composition and in vitro digestibility of dry matter. The sugar cane was homogenized with CaO levels 0, 0.75, 1.5, 2.25, 3.0, 3.75 and 4.5 percent, in natura matter, for 24 hours. The dry matter and mineral matter increased, while the organic matter of the sugar cane decreased (P <0.05) linearly as a result of the CaO levels. The CaO had no effect on the levels of crude protein and ether extract. The phosphorus concentration remained unchanged, but there was a significant increase (P<0.05) in the calcium content. The contents of neutral detergent fiber, acid detergent fiber and cellulose decreased linearly with the levels of CaO. The average levels of indigestible dry matter and indigestible neutral detergent fiber significantly decreased with increasing levels of CaO. The results showed that the in vitro dry matter digestibility (IVDMD) was different between fresh sugar cane and sugar cane with added levels of CaO from 1.5 percent. The IVDMD and nutritional value of the sugar cane was improved by adding 1.5 percent CaO based on fresh content...

O objetivo foi identificar o nível mais adequado de óxido de cálcio (CaO) no tratamento da cana-de-açúcar por meio da avaliação da composição química e a digestibilidade in vitro da matéria seca. A cana-de-açúcar foi homogeneizada adicionando os níveis de CaO 0; 0,75; 1,5; 2,25; 3,0; 3,75 e 4,5 por cento em porcentagem de matéria natural, por 24 horas. Os teores de matéria seca e matéria mineral aumentaram, ao passo que o teor de matéria orgânica da cana-de-açúcar diminuiu (P<0,05) de forma linear em função dos níveis de CaO. Não houve efeito dos níveis do CaO sobre o teor de proteína bruta e extrato etéreo. Os teores médios de fósforo mantiveram-se inalterados, porém ocorreu um aumento (P<0,05) no teor de cálcio. Os teores de fibra em detergente neutro, fibra em detergente ácido e celulose diminuíram linearmente em função dos níveis de CaO. Os teores médios da matéria seca indigestível e da fibra em detergente neutro indigestível tiveram redução significativa com o aumento dos níveis de CaO. Os resultados da digestibilidade in vitro da matéria seca (DIVDM) mostraram-se diferentes entre cana-de-açúcar in natura e a com níveis de CaO. Níveis de CaO a partir de 1,5 por cento melhoram o valor nutritivo e a DIVDM da cana-de-açúcar...

Paraganglioma gangliócítico do duodeno: relato de um caso / Gangliocytic paraganglioma of the duodenum: a case report

É apresentado um caso de paraganglioma gangliocítico da região da papila duodenal em paciente masculino de 51 anos, com queixa de dor epigástrica e empachamento pós-prandial. O paraganglioma gangliocítico é neoplasia rara no trato gastrointestinal, onde o local mais acometido é a região periampular do duodeno. A constituição por três tipos celulares permite sua identificação bem como diagnóstico diferencial com outros tumores um pouco mais comuns no local, como o carcinóide duodenal, o ganglioneuroma e o tumor estromal gastrointestinal (GIST).

CagA status and Helicobacter pylori eradication among dyspeptic patients.

AIM: Triple therapy seems more effective in curing Helicobacter pylori infection in patients with peptic ulcer than in those with non-ulcer dyspepsia. It has been suggested that this difference depends on the expression of CagA protein that is more frequent in the former. The objective of this study was to investigate a potential association between serum CagA positivity, severity of gastric mucosal inflammation and eradication success among peptic ulcer and non-ulcer dyspepsia patients. MATERIAL AND METHOD: Patients undergoing upper gastrointestinal endoscopy for investigation of dyspepsia at the Department of Gastroenterology, Hospital Vera Cruz, between March, 2000 and March 2001 were screened. H. pylori positive patients, as diagnosed by rapid urease test and histology were included. Severity of gastric mucosal inflammation was determined and serum CagA positivity was assessed using a commercially available ELISA assay prior to H. pylori 7-day eradication therapy with lansoprazole, clarithromycin and amoxicillin (30 mg, 500 mg and 1 g b.i.d., respectively). Eradication success was determined 8-24 weeks following completion of therapy. RESULTS: Seventy-four patients were included in the study (mean age 40.8, range 18-67, female = 28). CagA positivity was observed in 48% of patients. Gastroduodenal peptic ulceration was found in 54% of patients. Serum CagA positivity was significantly higher among peptic ulcer patients (62.5%), while CagA negativity was significantly higher among non-ulcer dyspepsia patients (67.7%). Lymphocyte and eosinophil infiltration was significantly higher among CagA + patients, despite being comparable when distributed among peptic ulcer and non-ulcer dyspepsia patients. Eradication was successful in 93.2% of patients, regardless of CagA status on a per protocol analysis. Based on a per protocol analysis, eradication success was comparable among peptic ulcer and non-ulcer dyspepsia patients, regardless of CagA status. CONCLUSION: Our results support the concept that CagA positivity is associated to peptic ulcer disease and to a higher severity of lymphocyte and eosinophil infiltration. Efficacy of treatment eradication of H. pylori may not be affected by serum CagA status.

Avaliação da atividade tóxica em Artemia salina e Biomphalaria glabrata de extratos de quatro espécies do gênero Eleocharis (Cyperaceae) / Toxic evaluation of four species of the genus Eleocharis (Cyperaceae) in Artemia salina and Biomphalaria glabrata

O gênero Eleocharis R. Br. compreende cerca de 200 espécies, ocorrendo em ambientes úmidos tais como brejos e margens de rios e lagos. Procurando novos agentes moluscicidas, os extratos de Eleocharis acutangula (Roxb.) Schult., Eleocharis interstincta (Vahl) Roem. & Schult., Eleocharis maculosa (Vahl) Roem. & Schult. e Eleocharis sellowiana Kunth foram testados para atividade moluscicida, contra caramujos adultos e desovas, e toxicidade (ensaio de letalidade com Artemia salina). O extrato hexânico de Eleocharis acutangula (parte subterrânea fresca) foi ativo contra Artemia salina (CL50 = 476,00 mg/mL), enquanto os demais extratos apresentaram CL50 >> 10³ mg/mL, sugerindo baixa toxicidade. O extrato hidro-etanólico de Eleocharis sellowiana (parte subterrânea fresca) foi ativo contra desovas de Biomphalaria glabrata (CL50 = 24,27 mg/mL) mas inativo contra indivíduos adultos. Os demais extratos testados não apresentaram atividade moluscicida.

The genus Eleocharis R. Br. comprises about 200 species, occurring in wet environments like swamps, lakes and river margins. In the search for new molluscicides, extracts from Eleocharis acutangula (Roxb.) Schult., Eleocharis interstincta (Vahl) Roem. & Schult., Eleocharis maculosa (Vahl) Roem. & Schult. and Eleocharis sellowiana Kunth were tested for molluscicidal activity (spawns and adult snails) and toxicity (Brine Shrimp Lethality - BSL - bioassay). The hexane extract of Eleocharis acutangula (fresh subterraneous parts) was active in the BSL bioassay (LC50 = 476 mg/mL), while the other extracts showed LC50 >> 10³ mg/mL, suggesting they have low toxicity. The aqueous ethanol extract of Eleocharis sellowiana (fresh subterraneous parts) was active against Biomphalaria glabrata spawns (LC50 = 24.27 mg/mL) but it was not lethal to adult snails. No other plant extract tested in this study showed molluscicidal activity.

Efficacy and tolerability of pantoprazole versus ranitidine in the treatment of reflux esophagitis and the influence of Helicobacter pylori infection on healing rate.

Patients with reflux esophagitis (grade II or III, Savary-Miller, intention-to-treat, n=256, age range 19-82 years) were randomly assigned to a double-blind, double-dummy treatment with either pantoprazole 40 mg once daily or ranitidine 150 mg twice daily. After 4 weeks, each patient was clinically and endoscopically assessed. Failure to heal required a further 4 weeks of treatment and a new evaluation thereafter. After 4 weeks, healing of lesions was confirmed in 63% (69 out of 109) of patients receiving pantoprazole and in 22% (25 out of 113) receiving ranitidine (P < 0.001, per protocol population). After 8 weeks, the cumulative healing rates were 88% and 46%, respectively (P < 0.001). Complete freedom from esophagitis-related symptoms (acid eructation, heartburn, pain while swallowing) was greater in the pantoprazole than in ranitidine group after 2 and 4 weeks (74% vs. 47%; 87% vs. 52%, respectively, P < 0.001). After 4 weeks, the healing rate was 76% in Helicobacter pylori (Hp)-positive vs. 45% in Hp-negative patients treated with pantoprazole (P < 0.01). The Hp status did not influence healing rates in patients treated with ranitidine. The most frequent adverse events in the pantoprazole group were diarrhea and somnolence (2-3% of patients), and in the ranitidine group, headache, diarrhea, dizziness, increase of liver enzymes and pruritus (2-4% of patients). In conclusion, pantoprazole was more effective than ranitidine in the healing rate and relief from reflux esophagitis-associated symptoms, and Hp infection was associated with higher healing rate during therapy with pantoprazole but not with ranitidine.

Prenylated flavonoids from Deguelia hatschbachii and their systematic significance in Deguelia.

Chemical investigation of dichloromethane and petrol extracts from the roots of D. hatshbachii A. M. G. Azevedo furnished thirteen compounds from which five are described for the first time and their structures were determined to be 3-(4'-hydroxyphenyl)-5-methoxy-6-( 3,3-dimethylallyl)-2"2"-dimethylchromene-(5",6":8,7)-3-(propyl-2-one)-4H-1-benzo-2,3-dihydropyran-2,4-dione; 6,4'-dihydroxy-3-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":5,4)-2-methoxy deoxybenzoin; 6.4'-dihydroxy-3-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":5,4)-2-methoxy-8-(propyl-2-one) deoxybenzon; 6-(3,3-dimethylallyl)-2",2"-dimethylchromene (5",6":4.5)-4'-hydroxy-3-methoxy stilbene and 3,5-dimethoxy-4'-hydroxy-4-(3,3-dimethylallyl) stilbene by spectral analysis (UV, IR, MS and ID- and 2D- NMR experiments). The root extracts and some isolated compounds were bioactive, as revealed by bioautography and brine shrimp lethality assays.

[Centipede stings notified by the "Centro de Informações Toxicológicas de Belém", over a 2-year period]. / Acidentes por centopéia notificados pelo "Centro de Informações Toxicológicas de Belém", num período de dois anos.

Centipedes are arthropods of the class Chilopoda. The objective of this work was to study the incidence of accidents involving centipedes at "Centro de Informações Toxicológicas de Belém" (CIT-Belém) over a two-year period. Seventy-six patients were studied from March 30, 1998 until March 30, 2000. Centipede accidents occurred in 16.8% of all accidents by venomous animals at Centro de Informações Toxicológicas de Belém; compared to snake accidents, 44.4 % and scorpion accidents, 20.5%. The majority of cases occurred in the residence (86.8%). The most important age group was 20-49 years old (64.4%). The part of human body mostly affected was the superior members (47.4 %). Local pain and edema were found in 95.8% and 52.1% of the patients, respectively. Treatment was symptomatic. Healing occurred in 94.7%, although the outcome of 5.3% of cases was unknown. Centipede accidents are a benign accident, occurring within the residence and treatment consists of measures to decrease the pain.

Flavonoids from Lonchocarpus latifolius roots.

From the petrol extract of Lonchocarpus latifolius roots, 10 flavonoids were isolated. These included: 3,5-dimethoxy-2'',2''-dimethylpyrano-(5'',6'':8,7)-flavone, 3-methoxy-(2'',3'':7,8)-furanoflavanone, 3',4'-methylenedioxy-(2'',3'':7,8)-furanoflavanone, and (2,3-trans-3,4-trans)-3,4-dimethoxy-(2'',3'':7,8)-furanoflavan, as well as the previously known karanjachromene, karanjin, lanceolatin B, pongachromene, pongaglabrone and ponganpin. Only nine flavonoids could be quantified through HPLC analysis.

Antireflux surgery followed by bipolar electrocoagulation in the treatment of Barrett's esophagus.

BACKGROUND: Management of Barrett's esophagus requires reduction of gastric acid secretion and screening for the development of adenocarcinoma. However, the current therapeutic options are ineffective in reducing the Barrett's mucosa. The aim of this study was to evaluate the effectiveness of endoscopic thermal coagulation of Barrett's mucosa as an alternative therapeutic approach and the recurrence of the disease in the long term. METHODS: Fourteen patients (11 men, 3 women; mean age 45.7 years) with Barrett's esophagus participated in the study. They underwent laparoscopic fundoplication and were symptom free with no defective fundoplication wraps before therapeutic endoscopy. Endoscopic thermocoagulation was performed with a flexible videoendoscope and a bipolar probe. Mucosal areas were treated once a month until the Barrett's mucosa disappeared. Endoscopy was performed 1 and 7 months after completion of the treatments and once a year thereafter. RESULTS: The mean follow-up period was 21.6 months (range 18 to 30 months). The mean length of Barrett's esophagus was 4.8 cm. Successful ablation of the columnar epithelium was achieved in 3.7 sessions, as defined by demonstration of normal squamous epithelium at histologic examination of biopsy samples collected after completion of the treatments and at follow-up evaluations. Three patients experienced short-term (10 days) odynophagia or dysphagia. All patients were symptom free with no evidence of Barrett's esophagus at the end of the study. CONCLUSIONS: Bipolar electrocoagulation after antireflux operations is effective in promoting regression of Barrett's esophagus and has few complications. Endoscopic thermal coagulation might reduce risk for adenocarcinoma among these patients.

Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation.

The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.

Acid suppression with ranitidine plus oral triple therapy improves ulcer healing but not Helicobacter pylori eradication.

BACKGROUND/AIMS: To evaluate whether the addition of 2 weeks of ranitidine to a 1-week oral triple therapy (OTT) regimen improved ulcer healing and H. pylori eradication. METHODOLOGY: Two hundred and eleven consecutive patients with an endoscopic diagnosis of active duodenal ulcer (DU) and a positive antrum biopsy for H. pylori were enrolled. Those attending the Hospital Vera Cruz (Group A, n=142) received a 14-day course of ranitidine (150 mg after breakfast and dinner) plus a 1-week OTT, consisting of bismuth subcitrate, (240 mg after the 3 meals), tetracycline (500 mg, 10 min before the three meals and at bedtime), and furazolidone (200 mg after breakfast and dinner). Patients from the Hospital das Clinicas (Group B, n=69) received the same OTT as Group A but without ranitidine. Patients underwent endoscopy again on average 40 days (range: 30-60 days) after completing therapy in order to assess ulcer healing and H. pylori status. RESULTS: Both schedules were equally efficient in eradicating H. pylori with 90% (128/142) eradication in group A, and 84% (58/69) in group B (p=0.2). In contrast, the addition of ranitidine to OTT improved ulcer healing when compared with OTT alone (96%, 137/142, vs. 70%, 48/69; p<0.001). CONCLUSIONS: Our results demonstrate that the association of acid suppression, obtained with 2 week ranitidine administration with OTT improved ulcer healing but did not enhance H. pylori eradication.

Plasma hydroxy-metronidazole/metronidazole ratio in patients with liver disease and in healthy volunteers.

Metronidazole pharmacokinetics were studied in patients with different degrees of liver cirrhosis, classified according to the Child-Pugh algorithm (A, B or C, as liver disease severity increases) and in schistosomic patients. Metronidazole (500 mg) was administered i.v. as a slow infusion over 20 min, and blood samples were collected at set intervals after the end of the infusion. The plasma concentrations of metronidazole and its main metabolite hydroxy-metronidazole were quantified by reversed-phase h.p.l.c. with u.v. detection. The metronidazole and hydroxy-metronidazole areas under the curve from 0 to 24 h (AUC0,24h), the metronidazole terminal elimination half-life (t1/2), the total clearance (CL), the metronidazole volume of distribution (V) values and the hydroxy-metronidazole/metronidazole concentration ratios as a function of time were calculated for each group. Comparison of the metronidazole AUC0,24h, t1/2 and CL values revealed that metronidazole metabolism is progressively impaired as the severity of liver disease increases. There were no variations in these parameters between the schistosomic and Child-Pugh A groups. In addition, there were no differences in the V and hydroxy-metronidazole AUC0,24h among the various groups studied. However, metronidazole metabolism was delayed in patients with hepatic disease, as illustrated by the hydroxy-metronidazole/metronidazole ratio 10 min after the end of metronidazole infusion. These results indicate that the clinical assessment of liver disease is paralleled by an impairment of metronidazole metabolism. Of the studied variables, we propose the hydroxy-metronidazole/metronidazole ratio 10 min after metronidazole infusion as a suitable and practical index for liver function evaluation.