Nous étudions la faisabilité du procédé de distillation extractive continue pour séparer des mélanges azéotropiques A-B à température de bulle minimale ou maximale, avec un tiers corps E lourd ou léger. Les mélanges ternaires A-B-E appartiennent aux classes 1.0-1-a et 1.0-2 qui se subdivisent chacune en deux souscas selon la position de la courbe d'univolatilité. La colonne de distillation a trois sections, rectification, extractive, épuisement. Nous établissons les équations décrivant les profiles de composition liquide dans chaque section en fonction des paramètres opératoires: pureté et taux de récupération du distillat, taux de reflux ratio R et rapport des débits d'alimentation FE/F dans le cas d'un tiers corps lourd ; pureté et taux de récupération du produit de pied, taux de rebouillage S et rapport des débits d'alimentation FE/F dans le cas d'un tiers corps léger. Avec un tiers corps lourd alimenté comme liquide bouillant au dessus de l'étage d'alimentation du mélange A-B, nous identifions le distillat atteignable et les plages de valeurs faisables des paramètres R et FE/F à partir du critère général de faisabilité énoncé par Rodriguez-Donis et al. (Ind. Eng. Chem. Res, 2009, 48(7), 3544–3559). Pour la classe 1.0-1a, il existe des rapport FE/F et reflux ratio minimum. Le rapport FE/F est plus important pour le procédé continu que pour le procédé discontinu parce que la faisabilité du procédé continu nécessite que les profils d'épuisement et extractifs s'intersectent. Pour la classe 1.0-2, les deux constituants A et B sont des distillats potentiels, l'un sous réserve que le rapport FE/F reste inférieur à une valeur limite maximale. Le procédé continu exhibe également une valeur minimale de FE/F à un taux de reflux ratio donné, contrairement au procédé discontinu. Avec un tiers corps léger alimenté comme vapeur saturante sous l'étage d'alimentation du mélange A-B, nous identifions le produit de pied atteignable et les plages de valeurs faisables des paramètres S et FE/F à partir du critère général de faisabilité énoncé par Rodriguez-Donis et al. (Ind. Eng. Chem. Res, 2012, 51, 4643–4660). Comparé au cas des tiers corps lourds, le produit principal est obtenu en pied. Autrement, les comportements des classes 1.0-1a et 1.0-2 sont analogues entre les tiers corps léger et lourd. Avec un tiers corps léger, le procédé continu ajoute la contrainte que les profils de rectification et extractifs s'intersectent. La contrainte d'intersection des profils d'épuisement et extractif est partagée par les deux modes opératoires continu et discontinu. Ce travail valide la méthodologie proposée pour évaluer la faisabilité du procédé de distillation extractive continue et permet de comparer les tiers entre eux en termes de taux de reflux ratio minimum et de rapport de débit d'alimentation minimal / We study the continuous extractive distillation of minimum and maximum boiling azeotropic mixtures A-B with a heavy or a light entrainer E, intending to assess its feasibility based on thermodynamic insights. The ternary mixtures belong to the common 1.0-1a and 1.0-2 class ternary diagrams, each with two sub-cases depending on the univolatility line location. The column has three sections, rectifying, extractive and stripping. Differential equations are derived for each section composition, depending on operating parameters: distillate product purity and recovery, reflux ratio R and entrainer – feed flow rate ratio FE/F for the heavy case; bottom product purity and recovery, reboil ratio and entrainer – feed flow rate ratio for the light entrainer case. For the case with a heavy entrainer fed as a boiling liquid above the main feed, the feasible product and operating parameters R and FE/F ranges are assessed under infinite reflux ratio conditions by using the general feasibility criterion enounced by Rodriguez-Donis et al. (Ind. Eng. Chem. Res, 2009, 48(7), 3544–3559). For the 1.0-1a class, there exists a minimum entrainer - feed flow rate ratio to recover the product, and also a minimum reflux ratio. The minimum entrainer - feed flow rate ratio is higher for the continuous process than for the batch because of the additional requirement in continuous mode that the stripping profile intersects with the extractive profile. For the 1.0-2 class both A and B can be distillated. For one of them there exists a maximum entrainer - feed flow rate ratio. The continuous process also has a minimum entrainer - feed flow rate ratio limit for a given feasible reflux ratio. For the case with a light entrainer fed as saturated vapor below the main feed, the feasible product and operating parameters S and FE/F ranges are assessed under infinite reflux ratio conditions by using the general feasibility criterion enounced by Rodriguez-Donis et al. (Ind. Eng. Chem. Res, 2012, 51, 4643–4660), Compared to the heavy entrainer case, the main product is removed from the column bottom. Similar results are obtained for the 1.0-1a and 1.0-2 class mixtures whether the entrainer is light or heavy. With a light entrainer, the batch insight about the process feasibility holds for the stripping and extractive sections. Now, an additional constraint in continuous mode comes from the necessary intersection between the rectifying and the extractive sections. This work validates the proposed methodology for assessing the feasibility of continuous extractive distillation processes and enables to compare entrainers in terms of minimum reflux ratio and minimum entrainer feed flow rate ratio

The aim of this thesis is to present a complex information about the etiology, diagnosis and treatment of gastroesophageal reflux disease (GERD) and to further elucidate the function of the diaphragm as the external esophageal sphincter and as a part of the antireflux barrier in patients with GERD. The study included 87 patients with verified GERD. Patients were subjected to a set of postural and respiratory maneuvers - caudal position of chest, abdominal breathing and measuring of the maximal respiratory pressures, all performed on the basis of tolerance to position and maneuver. The high-resolution manometry (HRM) was chosen to record the changes in pressure in the lower esophageal sphincter and for the measurement of respiratory pressures was used the spirometric system MasterScope. It was found that postural and respiratory maneuvers, that activate the diaphragm, increase the pressure in the EGJ. The most significant increase occurred during the maximal inspiratory maneuver, which increased LES pressure up to 261.2 %. The results also show that patients with GERD have reduced the strength of respiratory muscles, especially inspirational muscles. Reaching only 66.5 % of predicted PImax. We have demonstrated that patients with GERD have significantly lower diaphragm muscle strength, what...

Venous disease is a common vascular condition affecting the lower limbs and causes considerable morbidity in affected patients. National Health Service (NHS) treatment costs are substantial and there is a large demand for treatment much of which cannot be met. Roughly half a million people in the United Kingdom contact their general practitioner each year about varicose veins and associated clinical symptoms. In order to assign priorities and target interventions properly, authorities need to know which patients with venous disease will progress. Although many epidemiological studies have investigated the prevalence of venous disease, information on deterioration is scarce. The overall aim of this study is to determine the natural history of venous disease in the population and to identify lifestyle and clinical factors related to deterioration which might aid clinical decision making and health services policy. The specific objectives were to determine which risk factors were associated with deterioration of venous disease and venous reflux, and to ascertain the natural history of asymptomatic venous incompetence in terms of deteriorating to overt trunk varicose veins and chronic venous insufficiency. The study design was a population based cohort in the Edinburgh Vein Study which the survivors of the 1566 individuals aged 18 to 64 randomly sampled years from the general population at baseline underwent a 13-year follow-up examination. Details of the 1566 participants in the baseline study were sent to the Practitioner Services Division (PSD) of the NHS in Scotland who provided updated addresses and general practitioner registration details. Information collected on each subject at a follow-up clinic included lifestyle factors and medical history, height and weight measurement (by means of a questionnaire), clinical examination for classification of venous disease according to the Basle and CEAP systems, and duplex scanning to assess incompetence of venous valves in the deep and superficial systems of ten vein segments in each leg. Of the subjects from the baseline, 880 participated in the follow-up study, and 576 did not participate, providing a response rate of 60.4% of which 490 were female (55.7%) and 390 were male (44.3%). The study subjects were generally older and slightly more affluent than residents of the City of Edinburgh. For trunk varicose veins, the baseline prevalence was higher in males compared to females (p<0.01), but there was no difference in prevalence among subjects at the follow-up stage of the study (p=0.56). The overall rate of deterioration in trunk varicose veins was 3.55% per annum. More females than males deteriorated (p=0.04). Among subjects who showed deterioration in their trunk varicose veins, the commonest deterioration was from Basle Grade I (mild) at baseline to Grade II (moderate) at follow-up in both the right and left leg (28.1% and 32.9% respectively). Subjects older than 55 years of age (OR=1.59, 95% CI 1.01-2.51), who had a positive family history of varicose veins or venous ulcer (OR=1.92, 95% CI 1.20-3.07), and sat down at work for more than half the working day (OR=1.69, 95% CI 1.04-2.73) had increased risk of deteriorating trunk varicose veins. There was no significant difference between males and females in the prevalence of chronic venous insufficiency (CVI) among subjects at both the baseline and follow-up stage of the study (p=0.15 and 0.16 respectively). The rate of deterioration in CVI was 1.76% per annum. Similarly, among subjects who deteriorated, the commonest deterioration was from Grade I (mild) to Grade II (moderate) CEAP classification in both the right and left leg (42.4% and 45.5% respectively). The risk of worsening of CVI among those older than 55 was nearly three times more than those aged less than 55 (OR=2.85, 95% CI 1.18-6.87), and was still significant when adjusted for gender. The prevalence of telangiectasia was higher in females than in males in both the baseline and follow-up stages of the study (both p<0.01). The rate of deterioration in telangiectasia was 1.6% per annum. The commonest deterioration was from grade I (mild) at baseline to grade II (moderate) follow-up in the left and right leg (using the Basle Classification). Females subjects (OR=1.87, 95% CI 1.35-2.64), those older than 55 (OR=1.68, 95% CI 1.19-2.36), with a positive family history of venous disease (OR=1.60 95% CI 1.14-2.24) were associated with an increased risk of deterioration from telangiectasia compared to male subjects under 55 years of age and with no family history of the disease. The risk of telangiectasia deterioration was more than twice as high in subjects with venous reflux in the greater saphenous vein (origin) (OR=2.34, 95% CI 1.53-3.57), the greater saphenous vein (lower third of the thigh) (OR=2.28, 95% CI 1.59-3.27) and in the small saphenous vein (1.89, 95% CI 1.06-3.36) compared to those with no segments affected. The age and gender adjusted risk was also more than twice as high in subjects with venous reflux in two segments of the superficial system compared to subjects with no venous reflux in any segment (OR=2.06, 95% CI 1.23-3.44), and almost four times as high in subjects with reflux in more than three segments of the superficial system (OR=3.97, 95% CI 2.16-7.31) compared to subjects with no segments affected. On duplex scanning, the prevalence of reflux was higher in females than in males in the superficial system at baseline and follow-up stages of the study (p<0.01 respectively). In the deep system, the prevalence was higher in males than females at the baseline stage (p<0.01) with no significant difference at the follow-up stage (p=0.85). The rate of deterioration in venous reflux was 1.28% per annum. Most subjects deteriorated from one to two vein segments affected in the leg, the majority of which had reflux in the greater saphenous vein (thigh) at baseline and developed reflux in the greater saphenous vein (origin) at follow-up. Subjects more than 55 years of age had significantly more deterioration than those aged less than 55 (p<0.01). Obese or overweight subjects (OR=1.59, 95% CI 1.32-3.67), those aged more than 55 (OR=2.20, 95% CI 1.32-3.67), with a family history of varicose veins (among female subjects only, OR=2.55, 95% CI 1.16-5.56), and who sat down at work more than half the working time (among male subjects only) (OR=2.26, 95%CI 0.97-5.23) had increased risk of showing deterioration in reflux in any leg and in any vein segment from baseline to follow-up. Subjects with venous reflux at baseline were over two and half times more likely to show deterioration in trunk varicose veins compared to those with no reflux (OR=2.69, 95%CI 1.44-5.01), and four times more likely to deteriorate in either trunk varicose veins or chronic venous insufficiency (OR=4.20, 95% CI 2.42-7.29). Subjects with venous reflux at baseline were twice as likely to develop new trunk varicose veins (OR=2.08, 95%CI 1.25-3.46), and 1.78 times more likely to develop either trunk varicose veins or chronic venous insufficiency (OR=1.78, 95%CI 1.12-2.80). Age and gender adjusted risk of trunk varicose veins increased more than fourfold among subjects with venous reflux in the greater saphenous veins (OR=4.04, 95% CI 2.36-6.92), and more than threefold in the greater saphenous vein (lower third of the thigh) (OR=3.13, 95% CI 1.85-5.27) and the small saphenous vein (OR=3.17, 95% CI 1.55-6.48). Subjects with venous reflux in two or more than three vein segments in the superficial system were more than five times more likely to deteriorate from trunk varicose veins (OR=5.39, 95% CI 2.64-10.99 and OR=5.96, 95% CI 2.71-13.10 respectively). The Edinburgh Vein Study follow-up identified factors linked to deterioration of trunk varicose veins and CVI. The findings of this follow-up study have important implications in decision making in NHS and a prognostic tool could be produced to assist clinicians in deciding who should receive treatment or maintained under surveillance. Increasing age, and family history will likely lead to worsening of trunk varicose veins and CVI. The findings also confirm the association between asymptomatic and symptomatic venous valvular incompetence with worsening and developing new cases of venous disease. Such information will be essential for policy makers facing difficult decisions over prioritisation of services in the future. Further research might include trials of surgical and non-surgical interventions designed to limit deterioration in high risk individuals and enable surgeons to target interventions appropriately. Larger prognostic studies of many factors, including genotype, might be conducted to link progression of venous disease, and to provide further information on high risk individuals who might benefit from treatment.

Chronic Venous Insufficiency (CVI) is characterized by chronic venous hypertension from blood pooling in the lower limbs. The resulting symptoms include leg pain, varicose veins, fatigue, venous edema, skin pigmentation, inflammation, induration, and ulceration. Reflux from incompetent venous valves is a factor in up to 94% of individuals with CVI. Current treatments of CVI include compression stockings, drug therapy, vein disabling, venous stenting, and surgical correction with varying rates of success. However, a minimally invasive correction of deep venous reflux does not currently exist. A transcatheter prosthetic venous valve has the potential to be an effective, minimally invasive treatment for deep venous reflux which could treat up to 1.4 million individuals in the United States suffering from venous ulceration and make more than 1.7 billion dollars each year. Previously developed prosthetic venous valves have had problems with competency, patency, thrombogenicity, biocompatibility, and incorrect sizing. To meet the clinical need a prosthetic valve needs to be developed which succeeds where previous valves have failed. This thesis describes the design, analysis, pre-clinical testing, and evaluation of a novel prosthetic venous valve. Design specifications for an effective prosthetic venous valve were created. Verification tests were developed and performed which demonstrated that the valve met every design specification. Finite element and computational fluid dynamics simulations were performed to analyze the valve and calculated a maximum shear rate of 2300 s-1 in the valve during the high forward flow after a Valsalva maneuver. The valve is made of a biocompatible material that has low thrombogenicity, Poly(vinyl-alcohol) cryogel. On the average, the valve allows less than 0.5 mL/min of reflux at low and high retrograde pressures even after 500,000 cycles, indicating that it will reduce the reflux of individuals with venous reflux by more than 99.4%. The valve closes in less than 0.07 seconds and allows the distal pressure to rise to an average of 7% of the equilibrium pressure 30 seconds after a simulated ankle flexion. The valve increases the outflow resistance an average of 2.3 mmHg*min/L which is much less than obstruction levels,≥ 5 mmHg*min/L. The valve can fit in a 16 French catheter and is capable of percutaneous delivery. The base of the valve is 1.5 times the diameter of the vein in which it is to be implanted to help correct orientation upon deployment. Fluid behind the valve’s leaflets is ejected with a forward flow rate of 400 mL/min, suggesting that thrombus formation will not occur at this location. A stented valve remained patent in a porcine blood flow loop for 3 hours. The valve remains competent without buckling in a constricted vein at rest. The valve can expand to fit a vein with a maximum diameter 1.4 times the valve's initial diameter with low risk of tearing or leaflet prolapse. An IACUC protocol for a 12 week study to test the valve in sheep was prepared and approved. A study to evaluate the valve in humans is proposed with endpoints that can be tested for statistical significance and compared with other treatments for CVI. A set of valves which will correct reflux in the majority of common femoral, femoral, and popliteal deep veins is proposed and a sizing guide for surgeons is provided. The minimum distance between prosthetic valves placed in the same vein segment is 13 cm. A comparison of this valve with previously developed prosthetic venous valves and recommendations for work to be performed in the future are given. The valve proposed in this work is the only valve to meet all design specification for an effective prosthetic venous valve, and therefore shows great potential to be a minimally invasive treatment for deep venous reflux.

Thesis (PhD (Pathology. Anatomical Pathology))--University of Stellenbosch, 2006. / Patients with chronic gastro-oesophageal reflux disease are predisposed to Barrett’s metaplasia and oesophageal adenocarcinoma. The availability of molecular markers that can objectively identify patients with Barrett’s oesophagus at increased risk of carcinoma is highly desirable. A literature search was conducted to identify potentially useful biomarkers for genotype-phenotype correlation studies in South African patients with Barrett’s oesophagus. The COX-2, c-myb and c-myc genes selected for mRNA expression analysis were analysed in 26 patients with Barrett’s metaplasia (BM) without dysplasia; 14 with Barrett’s oesophagus and dysplasia (BD); 2 patients with Barrett’s adenocarcinoma (BAC); 19 with erosive oesophagitis (ERD); 25 with non-erosive oesophagitis (NERD) and 19 control individuals with a normal gastroscopy and no gastro-oesophageal reflux disease (GORD) symptoms. In the BD/BAC group, 69% (11/16) showed increased c-myb mRNA expression compared with 35% (9/26) in the BM group (p = 0.03). A statistically significant difference (p = 0.002) in c-myb expression was also observed between Barrett’s patients (20/42, 48%) and the control groups (9/63, 14%). In the BD patients, 21% (3/14) had increased c-myc mRNA expression compared with none in those with BM (p < 0.05) and BAC. No significant differences in mRNA expression levels were observed between ethnic groups for the genes analysed. In an attempt to determine whether the low expression level of c-myc in the study cohort may be related to possible gene-gene interaction, DNA samples of 199 individuals were subjected to genotyping of the functional GT-repeat polymorphism in the promoter region of the NRAMP1/SLC11A1 gene. Both these genes are involved in iron metabolism and c-myc is known to repress NRAMP1/SLC11A1. Genotype and allele frequencies were similar in all the groups studied with the 3/3 genotype being the most common. However, none of the three above-mentioned BD patients with increased c-myc mRNA expression had the 3/3 genotype. Therefore, although small in number, c-myc-NRAMP1/SLC11A1 interaction may be of adverse significance in patients with allele 2. TP53 mutation analysis was performed on 68 Barrett’s patients, and TP53 immuno-staining on oesophageal biopsy specimens of 55 subjects. Sporadic TP53 mutations were not identified in any of the patients with BM or dysplasia without BAC. Immuno-histochemistry staining of 2+ and 3+ intensity was similar in patients with metaplasia and dysplasia (58%). The low mutation frequency and relative non-specificity of TP53 immunostaining observed in Barrett’s patients seem to preclude its widespread use as a screening tool. TP53 mutation detection may however be useful for risk stratification once dysplasia has been diagnosed, as mutations G245R and D281Y were identified in two patients with BAC. Of the genes studied in the South African population, c-myb represents the most useful marker for early detection of an increased cancer risk in Barrett’s patients. In future, patients with Barrett’s oesophagus may benefit from genetic assessment to complement existing cancer surveillance and treatment strategies.

Les reflux laryngo-pharyngés acides, très fréquents en période néonatale, sont la remontée du contenu gastrique jusqu'au niveau du pharynx. Le contact entre un liquide (ex : liquide gastrique acide) et le larynx déclenche chez un nouveau-né à terme et en santé des mécanismes de défense (toux, déglutition, réaction d'éveil) appelés chémoréflexes laryngés, dont l'objectif est d'empêcher l'aspiration dans la trachée. Malheureusement, chez certains nouveau-nés, le contact entre le liquide et la muqueuse laryngée déclenche des réflexes délétères comprenant des apnées, des bradycardies et désaturations. Ces réflexes délétères sont impliqués dans les apnées du prématuré, les malaises graves du nourrisson et probablement dans certains cas du syndrome de mort subite du nourrisson.Les observations cliniques suggèrent que certaines conditions néonatales, dont la prématurité et une exposition post-natale à la fumée secondaire, favorisent la survenue de ces réflexes délétères. Ainsi, mon projet de doctorat consiste à étudier l'influence de la prématurité et l'influence d'une exposition à la fumée secondaire sur les CRL chez l'agneau nouveau-né. L'influence de la prématurité a été effectuée en utilisant un modèle d'agneau prématuré à 132 jours de gestation (terme = 147 jours). L'influence d'une exposition à la fumée secondaire post-natale, a, quant à elle, été effectuée en utilisant un modèle d'agneau exposé à la fumée secondaire durant les 16 premiers jours de vie à raison de 20 cigarettes/jour. Dans chaque étude, les agneaux ont été instrumentés pour enregistrer l'activité du muscle constricteur du larynx (muscle thyroaryténoidien), l'électroencéphalogramme, la fréquence cardiaque, la respiration et la saturation. Un cathéter supra-glottique a été utilisé pour l'injection de 0.5 ml de différentes solutions (modèle de prématuré : injection de sérum physiologique, d'eau distillée et HCl, pH 2; modèle d'exposition à la fumée secondaire : injection de sérum physiologique, d'eau distillée, HCl pH 2, lait) durant les différents stades de conscience. Le modèle d'agneau prématuré a permis de démontrer qu'une stimulation laryngée soit par l'eau distillée ou HCl à 7 jour post-natal induit des apnées prolongées, des bradycardies et des désaturations, lesquels sont potentiellement dangereuses. À l'inverse, une stimulation laryngée à 14 jours post-natals n'induit pas d'évènement cardiorespiratoire cliniquement significatif. Le modèle d'exposition à la fumée secondaire a, quant à lui, permis de démontrer qu'une exposition post-natale à la fumée secondaire induit une inhibition cardiorespiratoire plus importante et diminue les mécanismes de protection suite à une stimulation laryngée. Par contre, aucune stimulation n'entraîne d'évènement pouvant mettre en péril la vie de l'agneau. En conclusion, la survenue de réflexe potentiellement dangereux suite à une stimulation laryngée semble survenir en présence de certaines conditions néonatales. La prématurité semble être une de ces conditions.Les évènements potentiellement dangereux observés chez les agneaux prématurés montrent que les CRL sont probablement impliqués dans la pathogénèse des apnées/bradycardies du prématuré, phénomène fréquemment retrouvés en clinique. Quant à l'exposition à la fumée secondaire, elle est une condition néonatale qui modifie les réflexes obtenus suite à une stimulation laryngée sans induire de réflexes potentiellement dangereux.Les modifications observées suggèrent fortement que la fumée secondaire est un facteur de risque des malaises inopinés du nouveau-né et du syndrome de mort subite du nourrisson.

A Doença do Refluxo Gastroesofágico (DRGE), comumente observada em crianças e adolescentes, é uma das causas intrínsecas mais frequentes do desgaste erosivo. O objetivo dessa pesquisa foi realizar um estudo exploratório e analítico em crianças e adolescentes com idade entre 10 e 15 anos com DRGE e identificar possíveis diferenças entre grupos Casos e Controles quanto à presença de halitose, fluxo salivar, pH, capacidade tampão da saliva, lesões de desgaste erosivo e cárie dentária, classificação socioeconômica e qualidade de vida. Trinta voluntários participaram da pesquisa, sendo 15 do grupo Caso e 15 do grupo Controle. Informações sexo e idade foram coletadas durante a anamnese. A presença de halitose foi verificada por meio de avaliação organoléptica. A avaliação salivar foi realizada pelo fluxo salivar estimulado e o pH e a capacidade tampão (técnica de Ericsson), medidos com um pHmetro digital. Para a classificação econômica, utilizou-se o Critério de Classificação Econômica Brasil 2014 (CCEB/2014). Os voluntários responderam um questionário sobre qualidade de vida, validado no brasil (Child-OIDP) para faixa etária de 11-14 anos de idade. Além disso, foi realizado exame clínico para detecção de desgaste erosivo e cárie dentária de acordo com os índices BEWE e ICDAS, respectivamente. Os dados foram analisados pelo software STATA 9. As variáveis categorizadas sexo, idade, halitose e classificação socioeconômica e as variáveis numéricas fluxo salivar, capacidade tampão e pH não apresentaram diferença estatística entre os grupos (p > 0,05). O grupo Caso apresentou diferença significativa comparado ao grupo Controle para as variáveis BEWE e ICDAS. Apenas o desgaste erosivo e a presença de lesões de cárie foram associados a DRGE. O BEWE e o ICDAS podem ser considerados métodos auxiliares para o diagnóstico de pacientes com refluxo patológico. A relação interdisciplinar entre os profissionais de saúde, em especial, cirurgiões dentistas e médicos gastroenterologistas, é essencial para melhor conduta médica-odontológica de pacientes com Doença do Refluxo Gastroesofágico. / Gastroesophageal Reflux Disease (GERD), commonly observed in children and adolescents is one of the most common intrinsic causes of the erosive wear. The aim of this research was to conduct an exploratory and analytical study in children and adolescents aged between 10 and 15 years with GERD and to identify possible differences between Cases and Controls groups for the presence of halitosis, salivary flow, pH, saliva buffering capacity, erosive wear and dental caries, socioeconomic classification and quality of life. Thirty volunteers participated in this study, but fifteen were in the Case group and fifteen were in the Control group. Information about age and sex were collected during the anamnesis. The presence of halitosis was verified by organoleptic evaluation. The salivary tests were performed by saliva stimulated salivary flow; pH and buffering capacity (by Ericsson technique) were measured with a digital pH meter. Economic classification was evaluated by Economic Classification Criteria Brazil 2014 (CCEB/2014). The volunteers answered a questionnaire about quality of life, validated in Brazil (Child-OIDP) for the age group of 11-14 years. Furthermore, the clinical examination was conducted to erosive wear and caries detection in accordance with BEWE and ICDAS index, respectively. The data were analysed by Stata 9.0 software. Categorical variables sex, age, halitosis and socioeconomic classification and numeric variables salivary flow, buffer capacity and pH had not statistical difference between groups (p > 0.05). The Case group had significant difference compared to the Control group using BEWE and ICDAS variables. Only erosive tooth wear and carious lesions were associated with GERD. The BEWE and ICDAS can complement the methods for the diagnosis of patients with pathological reflux. The interdisciplinary relationship between dentists and gastroenterologists is essential for better medical and dental management of patients with Gastroesophageal Reflux Disease.

O refluxo vésico-ureteral (RVU) é uma das condições urológicas comumente diagnosticada entre crianças. Altos graus dessa condição podem causar cicatrização renal, insuficiência renal e hipertensão arterial. A uretrocistografia miccional é o método mais comumente utilizado para o diagnóstico, no entanto, esse procedimento envolve sedação, cateterismo vesical e expõe a criança a uma quantidade significativa de radiação. A investigação metabolômica pode fornecer novos entendimentos sobre a doença e visa a descoberta de metabólitos específicos associados a ela. Assim, existe um potencial considerável para a implementação de perfil metabólico em análises clínicas. Dessa forma, buscou-se estabelecer uma alternativa não invasiva para identificar crianças com o RVU através da metabolômica. Para a investigação metabolômica alvo um método por eletroforese capilar acoplada ao espectrômetro de massas (CE-MS) com analisador to tipo ion trap foi desenvolvido e validado para a determinação de 27 aminoácidos em urina. Os parâmetros experimentais relacionados às configurações da interface CE-MS, eletrólito (BGE) e espectrômetro de de massas (MS) foram otimizados, proporcionando uma boa separação dos 27 aminoácidos, incluindo os isômeros L-leucina, L-isoleucina e L-alloisoleucina, em menos de 30 min. O líquido auxiliar (SHL) foi composto de 0,5% (v/v) ácido fórmico em 60% (v/v) água/metanol à uma vazão de 5 &#181;L min-1. O BGE consistiu de 0,80 mol L-1 de ácido fórmico e 15% (v/v) de metanol. Um procedimento de stacking por pH foi implementado para aumentar a detectabilidade (uma solução de NH4OH a 12,5% (v/v) foi injetada a 0,5 psi/9 s antes das amostras). O método foi validado de acordo com os protocolos FDA e ICH, exibindo parâmetros aceitáveis. A quantificação bem sucedida dos aminoácidos em amostras de urina de um estudo piloto do RVU foi alcançada. A avaliação estatística dos resultados mostrou que alguns dos aminoácidos avaliados podem carregar informações que possibilitam discriminar as amostras de urina entre os grupos teste e controle. Para a análise metabolômica global urinária, métodos por RPLC-MS e HILIC-MS foram otimizados. Cinco colunas com diferentes propriedades foram investigadas para RPLC e quatro colunas para HILIC; adicionalmente, foram investigados a influência dos aditivos e pH da fase móvel. As condições ótimas foram determinadas avaliando o formato de pico, a relação sinal-ruído, o tempo de retenção, o número de molecular features detectados e sua distribuição durante o gradiente de eluição. A melhor condição obtida para RPLC utiliza a coluna CSH C18 e fase móvel composta por 0,1% (v/v) ácido fórmico em água (A) e 0,1% (v/v) ácido fórmico em acetonitrila (B). Para HILIC, o melhor desempenho foi obtido com a coluna zwitteriônica ZIC-HILIC e fase móvel composta por 10 mmol L-1 acetato de amônio pH 6,8 (B) e 95% (v/v) acetonitrila e 5% 200 mmol L-1 acetato de amônio pH 6,8 (A). As amostras de urina dos grupos controle e teste foram submetidas à análise metabolômica global por RPLC-MS usando o método otimizado e por CESI-MS. Os resultados indicaram que diversas rotas metabólicas podem ter sido alteradas pelo RVU. Alteração dos níveis de carnitinas e acilcarnitinas, aminoácidos e derivados, purinas e outros foi observada. Ainda, a presença de acilcarnitinas na urina podem indicar danos mitocondriais e a diminuição de triptofano e aumento do ácido quinurênico indicam uma alteração no metabolismo do triptofano. / Vesicoureteral reflux (VUR) is one of the most commonly urologic conditions diagnosed among children. A high degree of this condition can cause kidney scarring, kidney failure and high blood pressure. Voiding cystourethrography is the standard method for diagnosis; however, this procedure involves sedation, bladder catheterization and exposes the child to a significant amount of radiation. Metabolomics has provided new insights about the disease and aims to discover specific metabolites associated with it. Thus, there is a considerable potential for the implementation of metabolic profile in clinical analyses. Thus, we attempted to establish a noninvasive alternative to identify children with VUR through metabolomics approach. For target metabolomics, a CE-MS method was developed and validated for the separation and quantitative analysis of 27 amino acids in urine. Experimental parameters related to the CE-MS interface (based on co-axial sheath liquid, SHL), background electrolyte (BGE) and mass spectrometer (MS) settings were optimized providing a good separation of 27 amino acids, including the isomers L-leucine, L-isoleucine and L-alloisoleucine, in less than 30 min. The SHL was composed of 0.50% (v/v) formic acid in 60% (v/v) methanol-water delivered at a flow rate of 5 &#181;L min-1. The BGE consisted of 0.80 mol L-1 formic acid and 15% (v/v) methanol. A pH stacking procedure was implemented to enhance sensitivity (a 12.5% (v/v) NH4OH solution was injected at 0.5 psi/9 s prior to samples). The proposed method was thoroughly validated according to FDA and ICH protocols exhibiting acceptable parameters. A successful quantification of amino acids in urine samples from the VUR cohort was achieved. The statistical evaluation of the results showed that some of the amino acids may carry information for the discrimination of the urine samples between the test and control groups. For untargeted metabolomics analysis, methods by RPLC-MS and HILIC-MS were optimized. Five columns with different properties were investigated for RPLC and four columns for HILIC; additionally, the influence of additives and pH of the mobile phase were investigated. The optimum conditions were determined assessing the peak shape, signal-to-noise ratio, retention time, number of molecular features detected and their distribution during the elution gradient. The best condition obtained for RPLC uses CSH C18 column and mobile phase composed by 0.1% (v/v) formic acid in water (A) and 0.1% (v/v) formic acid in acetonitrile (B). For HILIC, the best performance was obtained with the zwitterionic ZIC-HILIC column and mobile phase composed by 10 mmol L-1 ammonium acetate pH 6.8 (B) and 95% (v/v) acetonitrile and 5% (v/v) 200 mmol L-1 ammonium acetate pH 6.8 (A). Urine samples from the control and test groups were submitted to global metabolomics analysis by RPLC-MS using the optimized method and by CESI-MS. The results indicated that several metabolic pathways may have been altered by VUR. Changes of carnitine and acylcarnitine levels, amino acids and derivatives, purines and others was observed. Furthermore, the presence of acylcarnitines in the urine may indicate mitochondrial damage and the decrease of tryptophan and increase of the kynurenic acid indicate a change in the metabolism of tryptophan.

INTRODUÇÃO: Há relatos de ocorrência de displasia e adenocarcinoma esofágico em pacientes com esôfago de Barrett submetidos a tratamento cirúrgico com fundoplicatura bem sucedido, comprovado pela realização de pHmetria esofágica prolongada sem evidência de acidez em esôfago, o que sugere que pode ocorrer refluxo distal ao cateter de pHmetria, não detectado por esse método. Essa hipótese motivou o desenvolvimento de metodologia para avaliar a presença de refluxo 1cm acima da borda superior do esfíncter inferior do esôfago (EIE). OBJETIVO: Comparar a exposição ácida em 3 diferentes níveis: 5cm acima da borda superior EIE, 1cm acima da borda superior do EIE e em região intra-esfincteriana. CASUÍSTICA E MÉTODO: 11 pacientes com esôfago de Barrett, submetidos à fundoplicatura à Nissen para tratamento do refluxo gastroesofágico, sem sintomas de refluxo e com endoscopia e estudo radiográfico contrastado de esôfago sem sinais de recidiva, foram selecionados. Foram submetidos à manometria esofágica para avaliar a localização e a extensão do EIE. Realizou-se então pHmetria esofágica com 4 canais: canal A: 5cm acima da borda superior do EIE; canal B: 1cm acima; canal C: intraesfincteriano, na porção média entre a borda superior e inferior do EIE; canal D: em posição intragástrica. Avaliou-se o escore de DeMeester no canal A, para detectar refluxo patológico. Comparou-se o número de episódios de refluxo ácido, o número de episódios de refluxo prolongado e a fração de tempo com pH < 4,0 nos canais A e B. Comparou-se a fração de tempo de pH < 4,0 nos canais B e C. A fração de tempo com pH < 4,0 no canal D foi usada como parâmetro para não migração proximal do cateter. RESULTADOS: Houve maior número de episódios de refluxo e maior fração de tempo com pH < 4,0 no canal B do que no canal A, com significância estatística, sendo a mediana do tempo de exposição ácida menor que 1,5%. Por outro lado, houve menor fração de tempo com pH < 4,0 no canal B do que no canal C, sugerindo competência do esfíncter em conter o refluxo gastroesofágico. Um paciente apresentou refluxo patológico no canal A, apesar de não ter evidência até então de refluxo. Dois casos de adenocarcinoma esofágico foram diagnosticados nos pacientes do grupo estudado. CONCLUSÕES: A região 1cm acima da borda superior do EIE está mais exposta a acidez do que a região 5cm acima da borda superior do EIE, embora a exposição ácida seja em níveis bem reduzidos. A região 1cm acima da borda superior do EIE está menos exposta a acidez do que a região intraesfincteriana, demonstrando eficácia da fundoplicatura em conter o refluxo nesse nível / INTRODUCTION: There are reports of dysplasia and esophageal adenocarcinoma occurring in patients with Barrett´s esophagus after successful surgical treatment with fundoplication, confirmed with prolonged esophageal pH monitoring showing no acid in esophagus, suggesting that there might be reflux distal to the catheter, not detected by this method. This hypothesis led to the development of methodology to evaluate the occurrence of reflux 1cm above the upper border of the lower esophageal sphincter (LES). OBJECTIVE: Compare the acid exposition in three different levels: 5cm above the upper border of the LES, 1cm above the upper border of the LES and in the intrasphincteric region. CASUISTIC AND METHODS: 11 patients with Barrett´s esophagus, submitted to Nissen fundoplication as treatment for gastroesophageal reflux, with no symptoms of reflux and with endoscopy and contrasted esophageal radiograph, were selected. The patients underwent esophageal manometry to evaluate the location and extension of the LES. After that, they underwent a 4-channel pH monitoring: channel A: 5cm above the upper border of the LES; channel B: 1cm above the upper border of the LES; channel C: intrasphincteric, in the mid-portion between the upper and lower border of the LES; channel D: intragastric. The DeMeester score was assessed in channel A, to detect pathologic reflux. The number of reflux episodes, the number of prolonged episodes and the fraction of time with pH < 4,0 were compared in channels A and B. The fraction of time with pH < 4,0 was compared in channels B and C. The fraction of time with pH < 4,0 in channel D was used as a parameter to ensure no proximal migration of the catheter. RESULTS: There were more episodes of reflux and a higher fraction of time with pH < 4,0 in channel B than in channel A, with statistical significance. On the other hand, there was lesser fraction of time with pH < 4,0 in channel B than in channel C, suggesting competence of the sphincter in preventing gastroesophageal reflux. One patient presented pathologic reflux in channel A, besides no other evidence of that. Two cases of esophageal adenocarcinoma were diagnosed in the studied patients. CONCLUSIONS: the region 1cm above the upper border of the LES is more exposed to acid than the region 5cm above the upper border of the LES, although this exposure occurred in reduced levels. The region 1cm above the upper border of the LES is less exposed to acid than the intrasphincteric region

Introdução: O tratamento cirúrgico da doença do refluxo gastroesofágico (DRGE) possui excelente resultado na maioria dos pacientes. Porém, um grupo significante de indivíduos apresenta complicações ou recidiva dos sintomas, com impacto na qualidade de vida. Objetivos: Avaliar o grau de satisfação dos pacientes submetidos à fundoplicatura laparoscópica à Nissen, e comparar os resultados da aplicação do questionário GERD-HRQL de qualidade de vida pessoalmente e por via telefônica. Identificar fatores pré e pós-operatórios associados ao resultado do tratamento cirúrgico. Métodos: Foram selecionados 178 pacientes operados entre 2005 e 2009, no serviço de cirurgia do esôfago do HCFMUSP. Os pacientes foram convocados para consulta ambulatorial. Foram levantados os prontuários médicos para obtenção de dados pré-operatórios. No estudo foi feita a análise de dados epidemiológicos, cirúrgicos, endoscópicos e manométricos. Os pacientes foram divididos em grupos, e foi aplicado o questionário de qualidade de vida GERD- HRQL. Foi avaliada também a nota de melhora dos sintomas de 0 a 10, a intenção de fazer novamente a cirurgia e o uso atual de omeprazol. Os pacientes que não puderam comparecer ao ambulatório foram entrevistados por telefone. Resultados: 90 pacientes foram incluídos no estudo, 45 no grupo A (entrevista ambulatorial) e 45 no grupo B (entrevista telefônica). Houve diferença significante entre a pontuação média no questionário GERD-HRQL dos pacientes do grupo A (6,29) e B (14,09), p=0,002. Esse resultado também foi significante quando separados homens (p=0,018) e mulheres (p=0,049) de ambos os grupos. Porém, a nota de melhora dos sintomas (p=0,642) e a intenção de fazer novamente a cirurgia (p=0,714) foram iguais. Analisando-se somente os pacientes do grupo A, a correlação linear de Pearson não mostrou diferença estatística entre a pontuação no questionário GERD-HRQL e idade (p=0,953), IMC pré-operatório (p=0,607), IMC pós-operatório (p=0,498), pressão do esfíncter inferior do esôfago (PEM, p=0,651; PRM, p>0,999) e amplitude média de contração do esôfago distal (p=0,997). A correlação da pontuação média no questionário GERD-HRQL com número de pontos na hiatoplastia (p=0,857), presença de esofagite erosiva pré-operatória (p=0,867), tamanho da hérnia hiatal (p=0,867) e presença de distúrbio motor do esôfago (p=0,207) também não mostrou significância estatística. A presença de esôfago de Barrett maior que 1cm correlacionou-se com menor pontuação no questionário GERD-HRQL (p=0,035). O uso rotineiro de omeprazol foi marcador de menor satisfação com a cirurgia (p=0,034). Conclusões: A satisfação dos pacientes com o tratamento cirúrgico é de forma geral elevada. A aplicação do questionário GERD-HRQL mostrou pior qualidade-de-vida dos pacientes entrevistados por telefone, em comparação aos pacientes entrevistados pessoalmente no ambulatório. O uso rotineiro de omeprazol após a cirurgia esteve associado à menor satisfação com o tratamento cirúrgico da DRGE Não foram identificados fatores pré-operatórios que possam determinar pior resultado da fundoplicatura laparoscópica à Nissen, porém a presença de esôfago de Barrett no pré-operatório foi um marcador de maior satisfação dos pacientes operados / Introduction: The surgical treatment of gastroesophageal reflux disease (GERD) has excellent results in most patients. However, a significant group develops complications or recurrence of symptoms, with impact on quality-of- life. Objectives: Evaluate the satisfaction of patients submitted to laparoscopic Nissen fundoplication, and compare the results of the GERD-HRQL quality of life questionnaire applied in person and by telephone. Identify pre and postoperative factors associated with the outcome of the surgical treatment.. Methods: 178 patients operated by the esophageal surgery division at Hospital das Clínicas da Faculdade de Medicina da USP, between 2005 and 2009, were selected. Patients were invited to an ambulatory interview. Charts were reviewed, and preoperative data was obtained. Epidemiological, surgical, endoscopic, and manometric parameters were studied. Patients were divided in groups, and the GERD-HRQL questionnaire was used. We also evaluated the score of symptom improvement between 0 and 10, if the patient would do the surgery again and current use of omeprazole. Patients who could not come to the ambulatory were interviewed by telephone. Results: 90 patients were enrolled in the study, 45 in group A (ambulatory interview) and 45 in group B (telephonic interview). There was significant statistical difference between the average score in the GERD-HRQL questionnaire in groups A (6,29) and B (14,09), p=0,002. This result was also significant among men (0,018) and women (0,049) in both groups. However, the score of symptom improvement (p=0,642) and the intention of doing the surgery again (p=0,714) were equivalent. In group A patients, Pearson\'s linear correlation did not show statistical difference between the GERD-HRQL score and age (p=0,953), preoperative BMI (p=0,607), postoperative BMI (p=0,997), inferior esophageal sphincter pressure (PEM, p=0,651; PRM, p>0,999) and distal esophageal contraction pressure (p=0,997). The correlation between GERD-HRQL score and number of stitches in hiatoplasty (p=0,857), presence of preoperative erosive esophagitis (p=0,867), size of hiatal hernia (p=0,867) and presence of motor esophageal disturbances (p=0,207) did not show statistical significance. The presence of Barrett\'s esophagus larger than 1cm correlated with a lower score on GERD-HRQL questionnaire (p=0,035). The routine use of omeprazole was a marker of lower satisfaction with the surgical treatment (p=0,034). Conclusions: Patient satisfaction with surgical treatment is generally high. The GERD-HRQL questionnaire showed poorer quality-of-life of patients interviewed by telephone, compared to patients interviewed at the ambulatory. The routine use of omeprazole after surgery was associated with lower satisfaction with the surgical treatment. No preoperative factors were identified that could determine worst outcome after laparoscopic Nissen fundoplication, but the presence of Barrett\'s esophagus preoperatively was a marker of increased patient\'s satisfaction