Sidia M. Callegari-Jacques

The Impact of Gastric Bypass on Gastroesophageal Reflux Disease in Patients With Morbid Obesity: A Prospective Study Based on the Montreal Consensus

Objectives:To assess the impact of gastric bypass (GBP) on gastroesophageal reflux disease (GERD) based on Montreal Consensus. Methods:In this study, 86 patients (25 men; aging 38 ± 12 years; body mass index 45 [35–68 kg/m2]) were investigated for GERD before GBP and 6 months later. Esophageal and extraesophageal syndromes were assessed based on Montreal Consensus. Esophageal acid exposure and gastric pouch acidity were also evaluated. Results:Overall prevalence of GERD was 64% before GBP and 33% after GBP (P < 0.0001). Typical reflux syndrome (TRS) was present in 47 patients (55%) preoperatively and disappeared in 39 of them (79%) post-GBP. Out of 39 patients with no symptoms, 4 (10%) developed TRS postoperatively (P < 0.0001). The chief TRS complaint changed from heartburn pre-GBP (96%) to regurgitation post-GBP (64%). Esophageal mucosa improved in 27, was unchanged in 51, and worsened in 8 patients (P = 0.001) in regard of esophagitis. Extraesophageal syndromes were present in 16 patients preoperatively and in none but one post-GBP (P = 0.0003). GERD-related well being and use of proton pump inhibitors were both improved after GBP. Total acid exposure decreased from a median (interquartile range, 25%–75%) of 5.1% (range, 2–8.2) to 1.1% (range, 0.2–4.8), P = 0.0002. Most patients (86%) showed and acid gastric pouch in fasting conditions post-GBP. Conclusions:GBP ameliorated GERD syndromes in most patients 6 months after the procedure, resulting in quality of life improvement and less proton pump inhibitors usage. Whether regurgitation post-GBP corresponds to reflux disease or bad eating behavior deserves further studies.

Application of an African Ancestry Index as a genomic control approach in a Brazilian population.

Ten ancestry informative markers were investigated in 101 coronary artery disease patients and 102 healthy controls from a Southern Brazilian population, in order to determine if stratification occurs in this population. The degree of African admixture detected in this population was estimated to be as high as 6%, but no differences between cases and controls were observed. Using an African Ancestry Index (AAI) that estimates admixture at the individual level it was possible to remove from the samples those individuals with evidence of African admixture. Therefore we have shown that it is possible to control for population stratification by choosing individuals, without the loss of statistical power that occurs with the use of other methods of genomic control.

Nuclear Morphometric Analysis (NMA): Screening of Senescence, Apoptosis and Nuclear Irregularities

Several cellular mechanisms affect nuclear morphology which can therefore be used to assess certain processes. Here, we present an analytic tool to quantify the number of cells in a population that present characteristics of senescence, apoptosis or nuclear irregularities through nuclear morphometric analysis. The tool presented here is based on nuclear image analysis and evaluation of size and regularity of adhered cells in culture. From 46 measurements of nuclear morphometry, principal component analysis filtered four measurements that best separated regular from irregular nuclei. These measurements, namely aspect, area box, radius ratio and roundness were combined into a single nuclear irregularity index (NII). Normal nuclei are used to set the parameters for a given cell type, and different nuclear phenotypes are separated in an area versus NII plot. The tool was validated with β-gal staining for senescence and annexin or caspases inhibitor for apoptosis as well as several treatments that induce different cellular phenotypes. This method provides a direct and objective way of screening normal, senescent, apoptotic and nuclear irregularities which may occur during failed mitosis or mitotic catastrophe, which may be very useful in basic and clinical research.

The burdened life of adults with ADHD: impairment beyond comorbidity.

Since approximately 70% of adult patients with attention-deficit/hyperactivity disorder (ADHD) have at least one comorbid disorder, rating of impairment specifically attributable to ADHD is a hard task. Despite the evidence linking environmental adversities with negative outcomes in ADHD, life events measures have not been used to rate the disorder impairment. The present study tested for the first time the hypothesis that increased ADHD severity is associated with an increase in negative recent life events, independently of comorbidity status. The psychiatric diagnoses of 211 adult ADHD outpatients were based on DSM-IV criteria assessed through structured interviews (K-SADS-E for ADHD and ODD, MINI for ASPD and SCID-IV-R for other comorbidities). ADHD severity was evaluated with the Swanson, Nolan and Pelham rating scale (SNAP-IV) and recent life events with the Life Experience Survey. Higher SNAP-IV inattention and hyperactivity scores, female gender, lower socioeconomic status and the presence of comorbid mood disorders were associated with negative life events. Poisson regression models with adjustment for possible confounders confirmed the effect of inattention and hyperactivity severity on negative life events. Our results suggest that the negative life events experienced by these patients are associated to the severity of ADHD independently from comorbid psychiatric disorders.

Further blood genetic studies on Amazonian diversity—Data from four Indian groups

Information related to 31 protein genetic systems was obtained for 307 individuals affiliated with the Cinta Larga, Karitiana, Surui and Kararaô Indians of northern Brazil. In terms of genetic distances the Cinta Larga showed more similarities with the Karitiana (both are Tupi-speaking tribes), while at a more distant level the Surui clustered with the Kararaô. The latter, a Cayapo subgroup, showed a completely different genetic constitution from the other subgroups of this same tribe. Both the Kararaô and Karitiana are small, remnant populations, and their gene pools have presumably been severely affected by random and founder effects. These results were incorporated with those of 25 other Amazonian Indian tribes, and analysis by two multivariate techniques confirmed a previously observed geographical dichotomy, suggesting either that the Amazon river constitutes a barrier to north-south gene flow or that latitudinally different past migrations entered the region from the west.

DRD2 haplotype is associated with dyskinesia induced by levodopa therapy in Parkinson’s disease patients

AIM Dyskinesia and motor fluctuation are frequent and serious complications of chronic levodopa therapy in patients with Parkinsons disease. Since genetic factors could play a role in determining the occurrence of these problems, the aim of the present study was to investigate whether possible functional polymorphisms among DRD2 and ANKK1 genes are associated with the risk of developing dyskinesia and motor fluctuations in Parkinsons disease patients. PATIENTS & METHODS One hundred and ninety nine patients in treatment with levodopa were genotyped for the -141CIns/Del, rs2283265, rs1076560, C957T, TaqIA and rs2734849 polymorphisms at the DRD2/ANKK1 gene region. RESULTS Carriers of the TTCTA haplotype showed an increased risk for the presence of dyskinesia (p = 0.007; 1.538 [95% CI: 1.126-2.101]). CONCLUSION Our data suggest an influence of the DRD2/ANKK1 gene region on levodopa-induced dyskinesia.

Evolução da prevalência de parasitoses intestinais em escolares em Caxias do Sul, RS

Reports on the prevalence of intestinal parasitosis in Brazil have been local in nature, with descriptions of different populations, which makes comprehensive diagnosis difficult. With the aim of studying the variation in the prevalence of intestinal parasitosis among schoolchildren in Caxias do Sul, Rio Grande do Sul, over a 35-year period, 9,787 parasitological stool tests that had been performed using centrifugal sedimentation were evaluated. There were positive results from 5,655 samples (58%), and the most prevalent infestations were of Ascaris lumbricoides (47%), Trichuris trichiura (36%), Enterobius vermicularis (8%) and the protozoa Giardia lamblia (24%) and Entamoeba coli (20%). The overall prevalence diminished from 89% to 37%, indicating an average decrease of 1.4% per year. Reductions in prevalence were observed for Ascaris lumbricoides (61 to 26%) and Trichuris trichiura (38 to 18%). No significant change was observed for Giardia lamblia. The prevalence of Entamoeba coli increased from 29 to 46%. The decreases in helminth prevalence were probably due to infrastructure improvements and educational actions undertaken in schools.

Cannabinoid type-1 receptor gene polymorphisms are associated with central obesity in a Southern Brazilian population

The CB1 cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in energy balance control, stimulating appetite and increasing body weight in wasting syndromes. Different studies have investigated the relationship between polymorphisms of the cannabinoid receptor 1 (CNR1) gene and obesity with conflicting results. In the present study, we investigated the 1359G/A (rs1049353), 3813A/G (rs12720071) and 4895A/G (rs806368) polymorphisms in the CNR1 gene in a Brazilian population of European descent. To verify the association between these variants and obesity-related traits in this population, 756 individuals were genotyped by PCR-RFLP methods. The 4895G allele was associated with waist to hip ratio (WHR) (P = 0.014; P = 0.042 after Bonferroni correction). An additive effect with the GAA haplotype was associated with WHR (P = 0.028), although this statistical significance disappeared after Bonferroni correction (P = 0.084). No significant association was observed between the genotypes of the 1359G/A and 3813A/G polymorphisms and any of the quantitative variables investigated. Our findings suggest that CNR1 gene polymorphism is associated with central obesity in this Brazilian population of European ancestry.

Alu insertions versus blood group plus protein genetic variability in four Amerindian populations.

Background : Do the population relationships obtained using DNA or blood group plus protein markers remain the same or do they reveal different patterns, indicating that the factors which influence genetic variation at these two levels of analysis are diverse? Can these markers shed light on the biological classification of the Aché, a Paraguayan tribe which only recently established more permanent contacts with non-Indians? Subjects and methods : To consider these questions we typed 193 individuals from four Amerindian tribes in relation to 12 Alu polymorphisms (five of them never studied in these populations), while 22 blood group plus protein systems were studied among the Aché. These data were then integrated with those previously available (blood groups plus proteins) for the three other populations. DNA extraction and amplification, as well as the other laboratory procedures, were performed using standard methods currently in use in our laboratory. The genetic relationships were obtained using the D A distance, and the trees were constructed by the neighbour-joining method, both developed by M. Nei and collaborators. Reliability of the trees was tested by bootstrap replications. Other population variability values were also determined using Neis methods. Results : Alu polymorphism was observed in all populations and for most of the loci; in the seven systems from which we could compare our results with those of other Amerindian groups agreement was satisfactory. Unusual findings on the blood group plus protein systems of the Aché were a very low (5%) HP*1 frequency and the presence of the C W phenotype in the Rh blood group. The intertribal patterns of relationship and other aspects of their variation were remarkably congruent in the two sets ( Alu; blood group plus protein) of systems. Conclusions : The answer to the first question posed above is affirmative. However, the problem of whether the Aché derived from a Gê group that preceded the Guarani colonization of Paraguay, or are just a differentiated Guarani group, could not be answered with the genetic information available; the second hypothesis seems more likely at present, but the point to be emphasized is the striking genetic distinctiveness of the Aché as compared to other Amerindians.

Cytokine genes are associated with tuberculin skin test response in a native Brazilian population.

Tuberculosis was a major cause of population decline among Brazilian indigenous peoples and remains a leading cause of morbidity and mortality among them. Despite high BCG coverage, results of Tuberculin Skin Test (TST) reactivity have shown high rates of anergy in Amazonian Indians. Given the high prevalence of anergy in these populations and the fact that genetic host factors play an important role in susceptibility to Mycobacterium tuberculosis (MTB), the aim of this study was to evaluate the association of nineteen polymorphisms in fifteen genes related to immune response and anergy in the Xavante, an indigenous group from Brazil. A total of 481 individuals were investigated. TST anergy was observed in 69% of them. Polymorphisms in four genes showed absence or very low variability: SP110, PTPN22, IL12RB1 and IL6. IFNG +874 A/T heterozygotes and IL4-590 C/C homozygotes were more frequent in those individuals who presented a positive TST (prevalence ratios of 1.9 and 2.0 respectively). The risk of anergy was 1.5 in IL10-1082 G/G homozygotes when compared to carriers for the A allele. In indigenous groups such as the Xavante exposure to a variety of infections, associated with specific genetic factors, may disturb the T-helper 1 and T-helper 2 balance leading to increased immunological susceptibility.