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51.
José Wálter Huamán Verónica Aliaga Gemma Domenech Sebastián Videla Esteban Saperas 《Gastroenterologia y hepatologia》2014
Background and aims
Noncardiac chest pain (NCCP) often represents a diagnostic and therapeutic challenge. Given that gastroesophageal reflux disease (GERD) is the most common cause of NCCP, initial treatment with proton-pump inhibitors (PPI) has been proposed for all patients (PPI testing), reserving esophageal function testing solely for non-responders. The aim of the present study was to provide evidence on the clinical utility of PPI testing with high-dose pantoprazole in patients with NCCP.Patients and methods
We carried out a study of diagnostic performance with a cohort design in patients with NCCP, who had been assessed by the Cardiology Service. All patients underwent upper endoscopy, esophageal manometry, and 24 h esophageal pH monitoring before PPI testing with pantoprazole 40 mg every 12 h for 1 month. Before and after treatment, we assessed the severity (intensity and frequency) of chest pain, quality of life, and anxiety and depression by means of specific questionnaires. The diagnosis of GERD was based on a pathological finding of esophageal pH monitoring. A positive response to PPI testing was defined as an improvement in chest pain > 50% compared with the baseline score after 1 month of PPI therapy.Results
We included 30 consecutive patients (17 men/13 women) with a mean age of 49 years. Of these 30 patients, 20 with NCCP had GERD (67%, 95% CI: 47%-83%). A positive response to PPI therapy was observed in 13 of the 30 (43%) patients with NCCP: 11 of the 20 (55%) patients in the GERD-positive group and 2 of the 10 (20%) in the GERD-negative group. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PPI testing was 55%, 80%, 85%, 47% and 63%, respectively. A significant reduction in chest pain after pantoprazole therapy (P = .003) and a slight non significant improvement in anxiety and depression was achieved in the GERD-positive group as compared to the GERD-negative group.Conclusions
In NCCP, PPI testing with pantoprazole has a low sensitivity for the diagnosis of GERD, placing in doubt the strategy of reserving functional study to non-responders to antisecretory therapy. Esophageal function testing and accurate diagnosis would allow appropriate targeted therapy for all patients with NCCP. 相似文献52.
53.
R Sanmartín J Tor A Sanvisens JJ López A Jou R Muga I Ojanguren E Barluenga S Videla R Planas B Clotet C Tural 《HIV medicine》2014,15(4):203-212
54.
Darwich L Cañadas M Videla S Coll J Piñol M Cobarsi P Molina-López R Vela S García-Cuyás F Llatjos M Sirera G Clotet B;the HIV-HPV Can Ruti Team 《HIV medicine》2012,13(9):549-557
BACKGROUND: Genital infections with low-risk (LR) and high-risk (HR) human papillomavirus (HPV) genotypes are associated with ano-genital condylomata and anal squamous cell cancer. HPV-related pathologies in HIV-infected men are a serious concern. In this study, the prevalence of anal condylomata and their association with cytological abnormalities and HPV infection in the anal canal in HIV-infected men [men who have sex with men (MSM) and heterosexuals] were estimated. METHODS: This was a cross-sectional study based on the first visits of patients in the Can Ruti HIV-positive Men (CARH·MEN) cohort. Anal condylomata were assessed by clinical and proctological examination. Samples from the anal canal were collected for HPV genotyping and cytological diagnoses. RESULTS: A total of 640 HIV-infected men (473 MSM and 167 heterosexuals) were included in the study. The overall prevalence of anal condylomata was 25% [157 of 640; 95% confidence interval (CI) 21-28%]; in MSM it was 28% and in heterosexuals it was 15% [odds ratio (OR) 2.2; 95% CI 1.4-3.5]. In patients with anal condylomata, HPV infection in the anal canal was more prevalent (92% vs. 67% in those without anal condylomata; OR 8.5; 95% CI 3.2-22). This higher HPV prevalence involved at least two HPV genotypes (OR 4.0; 95% CI 2.2-7.1), mainly HR genotypes (OR 3.3; 95% CI 1.7-6.4). Similarly, the cumulative prevalence of HPV-6 and HPV-11 was higher in patients with anal condylomata (63% vs. 19% in those without anal condylomata). Having anal condylomata was associated with higher prevalences of cytological abnormalities (83% vs. 32% in those without anal condylomata; OR 6.9; 95% CI 3.8-12.7) and high-grade squamous intraepithelial lesions (HSILs) (9% vs. 3% in those without anal condylomata; OR 9.0; 95% CI 2.9-28.4) in the anal canal. CONCLUSIONS: HIV-infected men with anal condylomata were at risk of presenting HSILs and harbouring multiple HR HPV infections in the anal canal. Although MSM presented the highest prevalence of anal condylomata, heterosexual men also had a clinically important prevalence. Our findings emphasize the importance of screening and follow-up for condylomata in the anal canal in HIV-infected men. 相似文献
55.
Present knowledge points to horizontal transmission as the most significant mechanism for Junin virus maintenance in the main natural reservoirs, namely Calomys musculinus and Calomys laucha.The existence of naturally infected Akodon azarae, both within and outside the endemic area, as well as the finding that other species, ecologically and phylogenetically related to the main reservoirs, such as Akodon molinae and Calomys callidus, can experimentally develop persistent infections with virus shedding through fauces, suggest a potential role for these cricetids as alternative reservoirs.Furthermore, since those rodents inhabit the borders of the area in which Argentine Hemorrhagic fever is endemic, the risk of spread of this area is to be expected.Whether the establishment of Junin virus persistence in Calomys musculinus and other reservoirs depends on viral or host factors, such as a selective defect in L3T4+ lymphocytes as recently shown for mice, remains to be explored.Corresponding author 相似文献
56.
V B Junqueira K Simizu L Van Halsema O R Koch S B Barros L A Videla 《Xenobiotica; the fate of foreign compounds in biological systems》1988,18(11):1297-1304
1. Lindane (60 mg/kg) administered orally to rats increased liver cytochrome P-450 content and superoxide radical (O2-.) generation 24 h after treatment, while formation of thiobarbituric acid reactants and NADPH/ADP-supported microsomal chemiluminescence were significantly increased 4 h after treatment. 2. Hepatic superoxide dismutase (SOD) and catalase decreased 6 h after lindane treatment and SOD/O2-. ratio progressively decreased during 4 to 24 h after lindane treatment. 3. Morphological evidence of hepatic cell injury after lindane treatment was seen at all times studied, and appeared to increase with time. 4. Lindane administration results in time-dependent oxidative stress in liver which involves an early component (4-6 h) related to the reductive metabolism of lindane, and a late component (24 h) associated with the induction of cytochrome P-450; the biochemical changes correlated with the observed morphological lesions. 相似文献
57.
Federico Piero Manuel Mendizabal Ezequiel Ridruejo Fernando Herz Wolff Beatriz Ameigeiras Margarita Anders María Isabel Schinoni Virginia Reggiardo Ana Palazzo María Videla Cristina Alonso Luisa Santos Adriana Varn Sebastin Figueroa Cecilia Vistarini Raúl Adrover Nora Fernndez Daniela Perez Federico Tanno Nelia Hernndez Marcela Sixto Silvia Borzi Andres Bruno Daniel Cocozzella Alejandro Soza Valeria Descalzi Claudio Estepo Alina Zerega Alexandre de Araujo Hugo Cheinquer Marcelo Silva 《Liver international》2019,39(6):1033-1043
58.
Sebastián Videla Mounia Lahjou Pascal Guibord Zhengguo Xu Carles Tolrà Gregorio Encina Eric Sicard Artur Sans 《Drugs in R&D》2012,12(4):217-225
Background
Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. The data available on the pharmacokinetic profile of doxylamine in humans are limited, notwithstanding that this drug has been marketed in European countries for more than 50 years. In fact, no data on the effect of food on the pharmacokinetic parameters of doxylamine are available.Objective
The objective of this study was to evaluate the pharmacokinetic parameters of doxylamine following a single oral dose of doxylamine hydrogen succinate 25 mg in healthy human subjects under fed and fasting conditions.Study Design
This was a single-center, randomized, single-dose, laboratory-blinded, two-period, two-sequence, crossover study.Setting
The study was conducted in a phase I clinical unit.Subjects and Methods
A single oral dose of doxylamine hydrogen succinate 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under either fed conditions (high-fat, high-calorie food intake) or fasting conditions in each study period. The drug administrations were separated by a wash-out period of seven calendar days. Plasma samples were collected for up to 60 hours postdose, and plasma doxylamine concentrations were determined by a high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs, and 12-lead electrocardiography.Results
In total, 24 healthy subjects (12 male and 12 female) were included in the study. Doxylamine succinate 25 mg tablets exhibited similar oral bioavailability of doxylamine in the fasting state (mean maximum plasma drug concentration [Cmax] 118.21 ng/mL, coefficient of variation [CV] 19.2%; mean area under the plasma concentration time curve from time zero to time t [AUCt] 1746.97 ng · h/mL, CV 31.6%) and in the fed state (mean Cmax 120.99 ng/mL, CV 15.0%; mean AUCt 1712.20 ng · h/mL, CV 26.7%). No statistically significant between-treatment differences were observed for any of the pharmacokinetic parameters under study. The fed: fasting ratios of the geometric least squares means with corresponding 90% confidence intervals for Cmax and AUCt were within the range of 80–125%.Conclusion
High-fat, high-calorie food intake does not affect the kinetics of doxylamine in healthy subjects. The drug was safe and well tolerated by the subjects in this study. 相似文献59.
Sebastián Videla Jesús Cebrecos Mounia Lahjou France Wagner Pascal Guibord Zhengguo Xu Anna Cabot Mercedes Encabo Gregorio Encina Eric Sicard Artur Sans 《Drugs in R&D》2013,13(2):129-135
Background
Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of doxylamine are available, although this drug has been marketed in European countries for more than 50 years.Objective
The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinate after a single oral dose administration under fasting conditions in healthy human subjects.Study Design
This was a single-center, randomized, single dose, laboratory-blinded, two-period, two-sequence, crossover study.Setting
The study was conducted in a phase I clinical unit.Subjects and Methods
A single oral dose of doxylamine hydrogen succinate of 12.5 mg (equivalent to 8.7 mg of doxylamine base) or 25 mg (equivalent to 17.4 mg of doxylamine base) was administered to healthy volunteers under fasting conditions in each study period. The drug administrations were separated by a wash-out period of 7 calendar days. Blood samples were collected for up to 60 h post-dose, and plasma doxylamine levels were determined by an ultra high-performance liquid chromatography method with tandem mass spectrometry detection. Pharmacokinetic parameters were calculated using non-compartmental analysis. Dose proportionality was assessed based on the parameter area under the concentration–time curve (AUCt normalized). Safety was evaluated through assessment of adverse events, standard laboratory evaluations, vital signs and 12-lead electrocardiogram (ECG).Results
In total, 12 healthy volunteers (3 male; 9 female) were included in the study. Mean maximum observed plasma concentration (Cmax) and area under the concentration–time curve from time zero to time t (AUCt) of doxylamine hydrogen succinate 12.5 mg and 25 mg tablets increased linearly and dose-dependently [12.5 mg: mean Cmax 61.94 ng/mL, coefficient of variation (CV) 23.2 %; mean AUCt 817.33 ng·h/mL, CV 27.4 %; and 25 mg: mean Cmax 124.91 ng/mL, CV 18.7 %; mean AUCt 1630.85 ng·h/mL, CV 22.8 %]. Mean AUCt normalized was 815.43 ng·h/mL, CV 22.8 % for 25 mg. The dose-normalized geometric mean ratio (%, 12.5 mg/25 mg) of AUCt was 98.92 (90 % CI: 92.46, 105.83). The most common adverse event was somnolence.Conclusions
Exposure to doxylamine was proportional over the therapeutic dose range of 12.5–25 mg in healthy volunteers. Based on the results, a predictable and linear increase in systemic exposure can be expected. Doxylamine hydrogen succinate was safe and well tolerated. 相似文献60.