Low levels of adherence with proton pump inhibitor therapy contribute to therapeutic failure in gastroesophageal reflux disease.

To assess adherence to proton pump inhibitor (PPI) treatment and associated variables in patients with gastroesophageal reflux disease (GERD). Cross-sectional and prospective comprising 240 consecutive adult patients, diagnosed with GERD for whom continuous use of standard or double dose of omeprazole had been prescribed. Patients were ranked as ne-GERD (162: 67.5%) or e-GERD classified according to the Los Angeles classification as A (48:20.0%), B (21:8.6%), C (1:0.5%), D (1:0.5%), and Barrett's esophagus (7:2.9%). The Morisky questionnaire was applied to assess adherence to therapy and a GERD questionnaire to assess symptoms and their impact. Adherence was correlated with demographics, cotherapies, comorbidities, treatment duration, symptoms scores, endoscopic findings, and patient awareness of their disease. 126 patients (52.5%) exhibited high level of adherence and 114 (47.5%) low level. Youngers (P= 0.002) or married (O.R. 2.41, P= 0.03 vs. widowers) patients had lower levels of adherence; symptomatic patients exhibited lower adherence (P= 0.02). All other variables studied had no influence on adherence. Patients with GERD attending a tertiary referral hospital in São Paulo exhibited a high rate of low adherence to the prescribed PPI therapy that may play a role in the therapy failure. Age <60 years, marital status and being symptomatic were risk factors for low adherence.

Rickettsial infections of dogs, horses and ticks in Juiz de Fora, southeastern Brazil, and isolation of Rickettsia rickettsii from Rhipicephalus sanguineus ticks.

The present study was performed in an area endemic for Brazilian spotted fever (BSF) in Juiz de Fora, state of Minas Gerais, Brazil, during the years 2007 and 2008, when fatal cases of BSF (caused by Rickettsia rickettsii) were reported. Adult ticks (Acari: Ixodidae) identified as Rhipicephalus sanguineus (Latreille) and Amblyomma cajennense (Fabricius) were collected from dogs and horses, respectively, and tested by polymerase chain reaction (PCR). Overall, 13.1% of the Rh. sanguineus ticks and none of the A. cajennense were found to be infected with R. rickettsii. Two isolates of R. rickettsii were successfully established in Vero cell culture from two Rh. sanguineus ticks. An indirect immunofluorescence assay (IFA) using R. rickettsii antigens detected blood serological reaction to R. rickettsii in 67.9% (53/78) of dogs and 41.0% (16/39) of horses living in the study area. Larval offspring from two Rh. sanguineus engorged females, naturally infected by R. rickettsii, were reared to adult stage in the laboratory. All active stages (larvae, nymphs, adults) remained 100% infected by R. rickettsii, which was efficiently transmitted to naïve rabbits. Overall, the results of the present study indicate a potential risk for transmission of R. rickettsii to humans by Rh. sanguineus, an occurrence yet to be documented in Brazil.

Esophageal motility patterns are altered in older adult patients. / Los patrones de motilidad esofágica están alterados en pacientes adultos mayores.

INTRODUCTION AND AIMS: Since the 1960s, several studies have shown the effect of aging on esophageal motility, with inconsistent results. The aim of the present study was to evaluate the manometric results in older adult patients (=60 years of age) with an esophageal disorder and compare them with adults under 60 years of age. MATERIALS AND METHODS: A cross-sectional, retrospective study was conducted that included a sample of 1,175 patients (936 older adults and 239 non-older adults). The patients were evaluated and compared with respect to (i) sex, (ii) main complaint for which esophageal manometry was indicated, (iii) comorbidities, (iv) current medications, (v) smoking, and (vi) manometry results. RESULTS: Patient age ranged from 19 to 92 years (women made up 76.5% of the older adults and 72.8% of the non-older adults). Normal lower esophageal sphincter relaxation and normal peristalsis were more frequent in the non-older patient group (91.1% vs. 84.8% and 87.4% vs. 76%, respectively). The manometry results for the non-older adults vs. the older adults, respectively, were: achalasia (2.9% vs. 5.9%); hypercontractile disorder (9.2% vs. 10.4%); hypocontractile disorder (38.5% vs. 47.6%); and normal values (49.4% vs. 36.1%). After excluding the variables that could change esophageal motility, the results revealed significant differences between the two study groups. CONCLUSIONS: Esophageal manometry demonstrated statistically significant differences between the older adult and non-older adult study population evaluated.

Dietary habits, ethanol and tobacco consumption as predictive factors in the development of esophageal carcinoma in patients with head and neck neoplasms.

Patients with primary head and neck cancers have a higher risk of developing esophageal cancer. The aim of this study was to investigate esophageal cancer prevalence, its risk factors (ethanol and tobacco consumption) and dietary habits in patients with head and neck cancer. Three hundred and twenty-six adults with primary head and neck cancer were followed by a retrospective observational study in a general university hospital in Sao Paulo, Brazil. Flexible videoendoscopy with lugol chromoscopy was the method used to investigate esophageal cancer prevalence. All subjects were interviewed face-to-face, revealing detailed information about their tobacco and alcohol use, as well as their dietary habits. Thirty-six patients with esophageal cancer were diagnosed and the overall prevalence rate was 11.04%. Patients who developed second esophageal tumors had the following characteristics: earlier age of initial ethanol consumption (P < 0.05), longer duration period of ethanol consumption (P < 0.05) and higher weekly consumption rate (P < 0.05). There was an increased risk of esophageal carcinoma in those patients who both smoked and drank (P < 0.05). There was no association between carcinoma of the esophagus and dietary habits in patients who developed esophageal neoplasms, compared with those who did not. Prevalence rate of esophageal neoplasms was 11.04% in patients with head and neck carcinoma, whose ethanol consumption was associated with esophageal cancer. There was an increased risk between ethanol and tobacco consumption and esophageal carcinoma development. On the other hand, there was no association regarding dietary habits between patients who developed esophageal cancer and those who did not.

Detecção de anticorpos anti-Rickettsia rickettsii em cães residentes em área negligenciada no município de São Paulo, SP, Brasil / [Detection of anti-Rickettsia rickettsii antibodies in dogs living in a neglected area in São Paulo, SP, Brazil]

A febre maculosa brasileira (FMB), descrita inicialmente nos Estados Unidos como febre maculosa das Montanhas Rochosas, é uma antropozoonose relatada apenas no continente americano e causada pela bactéria Rickettsia rickettsii. No Brasil a transmissão ocorre sobretudo pela picada de carrapatos do gênero Amblyomma spp. A doença foi inicialmente descrita como de transmissão em áreas rurais e silvestres, no entanto áreas periurbanas e urbanas vêm apresentando casos, principalmente relacionados com a presença de humanos residindo em pequenos fragmentos de mata ciliar. O presente estudo teve por objetivo elucidar a dispersão da FMB nas proximidades dos reservatórios Guarapiranga e Billings, na cidade de São Paulo, SP. Para tanto, a presença de anticorpos anti-R. rickettsii, Rickettsia parkeri e Rickettsia bellii foi avaliada em cães atendidos nas campanhas de esterilização cirúrgica e residentes ao redor dos reservatórios. Foram coletadas amostras de 393 cães, e as amostras de soro foram analisadas pela reação de imunofluorescência indireta (RIFI), com ponto de corte de 1:64. Os títulos para R. rickettsii variaram de 256 a 4096, com positividade de 3,3% (13/393); para R. bellii, de 128 a 1024 e 4,1% (16/393) de positivos, e um único animal (0,25%) foi soropositivo para R. parkeri, com título de 128. Os achados permitem concluir que a região de estudo apresenta condições de se tornar uma possível área com casos de FMB, pois comporta fragmentação de Mata Atlântica, condições essas ideais para a manutenção do vetor do gênero Amblyomma já descrito na região, bem como para a presença da Rickettsia rickettsii circulante entre os cães, confirmada pela existência de anticorpos. Condutas referentes à conscientização da população por meio de trabalhos educacionais devem ser implantadas para a prevenção da doença na população da área.(AU)

Brazilian Spotted Fever (BSF), initially described in the United States as Rocky Mountain Spotted Fever, is an anthropozoonosis reported only in the Americas and caused by the bacterium Rickettsia rickettsii. In Brazil, transmission occurs mainly through tick bites of the genus Amblyomma spp. The disease was initially described as transmission of rural and wild areas; however, peri-urban and urban areas have been presenting cases, mainly related to the presence of humans residing in small fragments of riparian forest. The present study aimed to elucidate the dispersal of BSF near the Guarapiranga and Billings Reservoirs, in the city of São Paulo, SP. The presence of anti-R. rickettsii, Rickettsia parkeri and Rickettsia bellii antibodies were evaluated in dogs treated in surgical sterilization campaigns and residents around the Reservoirs. Samples were collected from 393 dogs and serum samples were analyzed by indirect immunofluorescence reaction (RIFI) with a cutoff of 1:64. The titles for R. rickettsii varied from 256 to 4096 with a positivity of 3.3% (13/393); for R. bellii from 128 to 1024 and 4.1% (16/393) of positive and a single animal (0.25%) was seropositive for R. parkeri with a titre of 128. The findings allow us to conclude that the study region has conditions to become a possible area with BSF cases, as it involves Atlantic Forest, ideal conditions for the maintenance of the vector of the genus Amblyomma already described in the region and the presence of circulating Rickettsia rickettsii among dogs, confirmed by the presence of antibodies. Conducts regarding the awareness of the population through educational work should be implemented to prevent the disease in the population of the area.(AU)

Jejunal flora of patients with megaoesophagus secondary to Chagas disease.

The jejunal flora of 15 patients with megaoesophagus secondary to Chagas disease was studied and compared with that of 15 control individuals. In addition to the serological reactions for Chagas disease (immunofluorescence and complement fixation reaction), all subjects were submitted to endoscopy and X-ray of the oesophagus, gastric secretory study and investigation of the jejunal flora. The mean bacterial counts (log10) of Chagas disease patients (4.14 +/- 2.15 c.f.u./ml) was significantly higher than those of the control group (2.83 +/- 1.34 c.f.u./ml). Aerobic bacteria were isolated from 14 Chagasic patients (maximum count 10(10) c.f.u./ml) and 7 controls (maximum count 10(5) c.f.u./ml). Anaerobes were isolated from 7 patients (maximum count 10(7) c.f.u./ml) and 1 control (10 c.f.u./ml). Controls and Chagas disease patients differed significantly in the maximum acid output, but there was no statistically significant relation between bacterial counts and maximum output.

Achalasia: a prospective study comparing the results of dilatation and myotomy.

BACKGROUND/AIMS: In a prospective and randomized clinical study, the operative method and dilatation in the initial stage of megaesophagus were evaluated. METHODOLOGY: Forty patients in the initial stage of megaesophagus, managed by forced hydrostatic dilatation of the cardia (20 patients-DILAT Group) or by esophagocardiomyotomy associated with esophagofundopexy (20 patients-Group OP) were followed-up for three years, in terms of clinical, radiographic, endoscopic, manometric and pH monitoring. RESULTS: 1) Both procedures can be performed without significant morbidity or mortality. 2) The two procedures are similar regarding ongoing suppression of dysphagia. 3) Radiologically, the methods are equivalent, since they promote significant elimination of contrast stasis and maintenance of the esophageal diameter. 4) Endoscopic follow-up did not differentiate the procedures in terms of the development of reflux esophagitis, with a rate of only 5% for each group of patients. 5) Manometry demonstrated that surgery produced a significantly greater reduction of the LESP as compared to dilatation, although the latter also determined a marked drop in the maximum basal pressure of the LES. 6) Neither procedure altered the length of the LES. 7) With prolonged esophageal pH monitoring, dilatation demonstrated a greater propensity for reflux as compared to surgery. CONCLUSION: Both methods offer benefits in the treatment of the initial stage of megaesophagus, although esophageal pH monitoring indicates that dilatation provokes a greater index of esophageal acid exposition time.

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive HIV-infected individuals with CD4 cell counts between 50 and 250/mm3.

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

[Gastroesophageal reflux disease: comparison between patients with and without esophagitis, concerning age, gender and symptoms]. / Doença do refluxo gastroesofágico: comparação entre as formas com e sem esofagite, em relação aos dados demográficos e às manifestações sintomáticas.

BACKGROUND: Patients with gastroesophageal reflux disease may or may not have endoscopic esophagitis; there are few studies comparing these groups among themselves. OBJECTIVES: This study was designed in order to evaluate differences between patients with gastroesophageal reflux disease with and without esophagitis. PATIENTS/METHODS: A hundred and twenty-two patients with gastroesophageal reflux disease characterized by esophageal endoscopy and pHmetry were included, 90 with and 32 without esophagitis. Assessment involved an anamnesis, including the following data: age, sex, heartburn, dysphasia, non-cardiac chest pain and respiratory symptoms. Heartburn was analyzed in more detail, its duration, intensity and periodicity being determined. RESULTS: No statistical significant difference was observed between the groups, regarding age, sex or presence of symptoms. However, in the group with esophagitis, heartburn classified as severe or very severe was more frequent. CONCLUSIONS: 1. The groups of patients with or without esophagitis analyzed were very similar concerning age, gender and presence of symptoms. However, regarding the heartburn's intensity, it was more intense in the group with esophagitis. 2. Among patients with gastroesophageal reflux disease, there is a large number of cases without esophagitis (26.2%) and that prolonged pH-monitoring is fundamental in its identification; 3. A better definition of reflux disease, esophagitis and pathological reflux is needed, in order to allow better diagnostic accuracy and comparisons in different studies on this subject.

The screening sensitivity of endoscopy, acid perfusion test and 24-hour pH-monitoring to evaluate esophagitis in patients with heartburn and histological esophagitis.

The sensitivity of endoscopic examinations, acid perfusion test and 24-hour esophageal pH-monitoring, were studied in patients with heartburn. Thirty six adult patients with histological esophagitis were included in this prospective study. Endoscopy showed esophageal lesion in 18/36 (sensitivity of 50%): esophagitis grade I in 10 (55.6%) and, grade II in eight (44.4%). Acid perfusion test was positive in 10/25 (sensitivity of 40%) of the patients submitted to the test. Twenty-four-hour pH-monitoring was positive in 17/29 patients (sensitivity of 58.6%): eight (61.5%) did not have esophageal lesion at endoscopy, two (25%) had esophagitis grade I and seven (87.5%) had esophagitis grade II. In the patients submitted to 24-hour pH-monitoring, a greater number or reflux episodes in orthostatic position than in supine position (P < 0.0001) was observed. The total number of reflux episodes, the most prolonged reflux and the total pH time < 4 were statistically higher in post-prandial period than during meals (P = 0.005).

The role of stress-related physical confinement in the pathogenesis of acute gastric hemorrhage after alcohol instillation in rats.

The combination of alcohol and stress have been considered producers of gastric hemorrhage both experimentally and in clinical observations. Since excessive alcohol intake often occurs in situations of severe emotional conflict and stress, it was decided to study the possible role of the latter in the etiology of gastric hemorrhage, up to now thought to be dependent only on alcohol. The study consists of 75 male Wistar rats divided into eight groups with seven to 14 animals each. They were submitted to fasting only, or to additional prolonged fasting, restraint-stress (physical confinement) for 17 hours and the oral administration of a single dose of 40% alcohol (1 ml/150 g of body weight). The stomachs were analyzed macroscopically and microscopically for the presence of gastric hemorrhage, and the following was observed; 1) only 10% of the rats submitted to a 25 hour fast either isolated or associated with 17 hours of physical confinement, demonstrated gastric hemorrhage; 2) after an eight hour fast, the administration of alcohol to the rats either sacrificed immediately or maintained for 17 hours, revealed gastric lesions in only 33.3% and 28.5% respectively, without significant statistical difference between the two groups (P > 0.05); 3) administration of alcohol prior to the 17 hour physical confinement revealed lesions in only 12.5% of the animals; 4) administration of alcohol to rats previously submitted to a 25 hour fast plus physical confinement for 17 hours, resulted in a significant number of hemorrhagic lesions (88.8%). This caused a statistical difference in the group compared to the others (P < 0.01). The results of this study led to the conclusion that stress (by prolonged physical confinement) was an important conditioning factor to the appearance of gastric hemorrhage when 40% alcohol was administered. It is possible that if the alcohol had been administered prior to the prolonged physical confinement its cytotoxic effect on the gastric mucosa might have been reduced.

Randomised clinical trial: daily pantoprazole magnesium 40 mg vs. esomeprazole 40 mg for gastro-oesophageal reflux disease, assessed by endoscopy and symptoms.

BACKGROUND: Pantoprazole magnesium (pantoprazole-Mg) may display extended inhibition of the proton pump with the potential for improved clinical efficacy in gastro-oesophageal reflux disease (GERD). AIM: To compare the efficacy of pantoprazole-Mg and esomeprazole in GERD. METHODS: Gastro-oesophageal reflux disease (Los Angeles grades A-D) patients were randomised to 4 weeks of treatment with pantoprazole-Mg (n = 290) or esomeprazole (n = 288), both 40 mg once daily, in this multicentre (14 Brazilian sites in 9 cities), double-blind study, with an additional 4 weeks' treatment in nonresponding patients. Severity of oesophagitis (at endoscopy) and GERD-related symptoms (ReQuest-GI) were assessed. The primary end point was the proportion of patients in complete remission (ReQuest-GI score <1.73 plus endoscopic healing) at week 4. RESULTS: Complete remission occurred in 61% of patients in each treatment group at 4 weeks (primary endpoint) and in 81% and 79% of patients in the pantoprazole-Mg and esomeprazole groups at 8 weeks, with no significant differences. Mucosal healing rates were high and not significantly different. At 8 weeks, symptom relief with pantoprazole-Mg was significantly greater than that with esomeprazole (91.6% vs. 86.0%, P = 0.0370) because of continued improvement in symptoms with pantoprazole-Mg from week 4 to week 8 (P = 0.0206). CONCLUSIONS: Pantoprazole-Mg 40 mg was at least as effective as esomeprazole 40 mg for complete remission and the mucosal healing rate was high. Symptom relief with pantoprazole-Mg continued to improve from 4 to 8 weeks and was greater than that with esomeprazole at week 8, suggesting an extended period of treatment effect (ClinicalTrials.gov identifier: NCT01132638).

Comparative evaluation of infected and noninfected Amblyomma triste ticks with Rickettsia parkeri, the agent of an emerging rickettsiosis in the New World.

The distribution of Rickettsia parkeri in South America has been associated with Amblyomma triste ticks. The present study evaluated under laboratory conditions two colonies of A. triste: one started from engorged females that were naturally infected by R. parkeri (designated as infected group); the other started from noninfected females (designated as control group). Both colonies were reared in parallel for five consecutive generations. Tick-naïve domestic rabbits were used for feeding of each tick stage and generation. R. parkeri was preserved by transstadial maintenance and transovarial transmission in A. triste ticks for five consecutive generations, because all tested larvae, nymphs, and adults from the infected group were shown by PCR to contain rickettsial DNA. All rabbits infested by larvae, nymphs, and adults from the infected group seroconverted, indicating that these tick stages were all vector competent for R. parkeri. Expressive differences in mortality rates were observed between engorged nymphs from the infected and control groups, as indicated by 65.9% and 92.4% molting success, respectively. Our results indicate that A. triste can act as a natural reservoir for R. parkeri. However, due to deleterious effect caused by R. parkeri on engorged nymphs, amplifier vertebrate hosts might be necessary for natural long-term maintenance of R. parkeri in A. triste.

Antibodies against rickettsiae from spotted fever groups in horses from two mesoregions in the state of Santa Catarina, Brazil / Anticorpos contra rickettsias do grupo da febre maculosa em equinos de duas mesorregiões de Santa Catarina, Brasil

Bacteria of the Rickettsia genus are agents of Brazilian Spotted Fever (BSF), a zoonotic disease which is difficult to diagnose, evolves quickly and can result in death. Antibodies against Rickettsia spp. in horses were studied, by means of Indirect Immunofluorescence Assay (IFAT ≥64), in 150 blood samples taken from animals in two Santa Catarina mesoregions (Planalto Serrano and Vale do Itajaí). The overall occurrence of Rickettsia spp. antibodies in horses was 18.66%, with cross-reactivity occurring in all positive samples for at least two of the species tested. Separately, according to the species, 25 (16.66%) samples were positive for R. rickettsii, 15 (10%) for R. parkeri, 22 (14.66%) for R. amblyommii, 23 (15.33%) for R. rhipicephali, 16 (10.66%) for R. bellii and 19 (12.66%) for R. felis. Only two animals resulted in a conclusive serodiagnosis, one for R. bellii and the other for R. rickettsii, at maximum dilutions of 1:4096 and 1:512, respectively. The occurrence of antibodies against Rickettsia spp. in horses from two mesoregions in the state of Santa Catarina indicates the movement of BSF agents in these sentinel animals and confirms the importance of studying spotted fever in the state of Santa Catarina.

Bactérias do gênero Rickettsia são agentes da Febre Maculosa Brasileira (FMB), uma doença zoonótica, de difícil diagnóstico, rápida evolução e que pode levar o indivíduo à morte. Anticorpos contra Rickettsia spp. em equinos foram pesquisados, por meio da Reação de Imunofluorescência Indireta (RIFI≥64), em 150 amostras de sangue colhidas de animais em duas mesorregiões de Santa Catarina (Planalto Serrano e Vale do Itajaí). A ocorrência de anticorpos contra Rickettsia spp. observada em equinos de duas mesorregiões de Santa Catarina foi de 18,66%, ocorrendo reações cruzadas em todas as amostras positivas para, no mínimo, duas das espécies testadas. Isoladamente, de acordo com as espécies, 25 (16,66%) amostras foram positivas para R. rickettsii, 15 (10%) para R. parkeri, 22 (14,66%) para R. amblyommii, 23 (15,33%) para R. rhipicephali, 16 (10,66%) para R. bellii e 19 (12,66%) para R. felis. Somente dois animais resultaram em um sorodiagnóstico conclusivo, um para Rickettsia bellii e outro para R. rickettsii, nas diluições máximas de 1:4096 e 1:512, respectivamente. A ocorrência de anticorpos contra Rickettsia spp. em equinos de duas mesorregiões de Santa Catarina indica a circulação de agentes da FMB nestes animais sentinela e ratificam a importância do estudo da febre maculosa no estado de Santa Catarina.