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Rocío Nú?ez-Torres Raquel M Fernández Manuel López-Alonso Guillermo Anti?olo Salud Borrego 《BMC medical genetics》2009,10(1):119-6
Background
Hirschsprung disease (HSCR) is a congenital malformation of the hindgut produced by a disruption in neural crest cell migration during embryonic development. HSCR has a complex genetic etiology and mutations in several genes, mainly the RET proto-oncogene, have been related to the disease. There is a clear predominance of missense/nonsense mutations in these genes whereas copy number variations (CNVs) have been seldom described, probably due to the limitations of conventional techniques usually employed for mutational analysis. 相似文献104.
Cristina Grávalos Carlos Gómez-Martín Fernando Rivera Inmaculada Alés Bernardo Queralt Antonia Márquez Ulpiano Jiménez Vicente Alonso Rocío García-Carbonero Javier Sastre Ramon Colomer Hernán Cortés-Funes Antonio Jimeno 《Clinical & translational oncology》2011,13(3):179-184
Introduction
HER2 over-expression and/or amplification are present in 9-38% of gastric or gastroesophageal junction (GEJ) cancers and are correlated to poor outcome. We conducted a multicentre phase II trial to evaluate trastuzumab in combination with cisplatin in patients with untreated HER2-positive advanced gastric or GEJ cancer.Materials and methods
Chemo-naïve patients with measurable, non-resectable, advanced or metastatic gastric or GEJ adenocarcinoma, with HER2 over-expression and/or amplification (IHC 3+, or IHC 2+ and FISH+), age ≥18 years, ECOG ≤2, left ventricle ejection fraction ≥50% and adequate organ function were eligible. Treatment consisted of trastuzumab (8 mg/kg on cycle 1 day 1 as loading; 6 mg/kg in subsequent cycles) and cisplatin (75 mg/m2), both intravenously on day 1, every 21 days.Results
Twenty-two out of 228 patients (10%) were HER2-positive and were included in this phase II trial. The median age was 66 years and ECOG 0/1 was 41%/59%. The median number of cycles was 4 (range 1–41). The confirmed ORR was 32% and disease control was achieved in 64% of patients. Median time to progression was 5.1 months. Grade 3 adverse events included asthenia (27%), neutropenia (18%), anorexia (14%), diarrhoea (9%) and abdominal pain (9%). There were no grade 4 toxicities or treatment-related deaths. Higher baseline HER extracellular domain (ECD) levels were associated with better outcome in terms of response and survival.Conclusions
Trastuzumab in combination with cisplatin is an active regimen and has a favourable toxicity profile in advanced HER2-positive gastric or gastroesophageal cancers. 相似文献105.
Objective: The CARDHIAC(R) (CARduran en pacientes Diabéticos con HIpertensi'on Arterial no Controlada) trial examined the effects of doxazosin gastrointestinal therapeutic system (GITS) and atenolol on 3 separate measures of target-organ damage-left ventricular mass index (LVMI), carotid intima media thickness (IMT), and urinary albumin excretion (UAE) in patients with type 2 diabetes mellitus and hypertension. Method: This trial had a prospextive, open-label, blinded-evaluation design and a duration of 9 months. Patients whose blood pressure (BP) was uncontrolled (systolic BP>/=130 mm Hg and/or diastolic BP>/=80 mm Hg) despite at least 1 month of treatment with a reninangiotensin blocker and diuretic were randomly allocated to receive doxazosin GITS 4 mg or atenolol 50 mg once daily in addition to their existing treatment. Seated BP was measured at study visits at 1, 3, 6 and 9 months; if the BP goal was not achieved at any visit, the dose of doxazosin or atenolol was titrated upward to 8 or 100 mg, respectively. Treatment complaince (pill count) and adverse reactions were monitored at each visit. Each patient underwent echocardiography and Doppler ultrasonography at baseline and at the end of the study for evaluation of the change in LVMI. The change in carotid IMT was evaluated by carotid ultrasound examination at the same time points. UAE also was measured at baseline and the end of the study. Results: Sixty patients (100% white; 51% female; mean [SD] age, 63.4 [7.5] years; body mass index, 28.2 [3.4] kg/m(2)) were randomized to receive doxazosin GITS (n=32) or atenolol (n=28) .At baseline, mean BP was 150.2 (10.6)/90.1 (7.3) mm Hg in the doxazasin group and 153.1 (13.8)/92.3 (6.1) mm Hg in the atenolol group (P=NS). At the end of the study, BP had decreased by 10.1 (3.2)/5.2 (1.3) mm Hg in the doxazosin group and 12.2 (4.2)/6.3 (2.1) mm Hg in the atenolol group (both, P<0.001 vs baseline; P=NS between groups). Heart rate at the end of the study was 78(6) beats/min in the doxazosin group (P=NS vs baseline) and 66(7) beats/min in the atenolol group (P < 0.01 vs baseline and between groups). LVMI decreased by 10.8 in the doxazosin group (P=0.001 vs baseline) and 4.2% in the atenolol group (P=NS vs baseline; P=0.03 between groups). The changes in carotid IMT and UAE were not statistically significant between groups. Conclusions: In this study in hypertensive patients with type 2 diabetes, LVMI was significantly decreasded in doxazosin-treated patients relative to baseline and compared with atenolol-treated patients. The differences in carotid IMT and UAE were not statistically significant between groups. 相似文献
106.
Rocío de la Puerta Ana Marquez-Martin Angeles Fernandez-Arche Valentina Ruiz-Gutierrez 《Nutrition (Burbank, Los Angeles County, Calif.)》2009,25(5):548-554
ObjectiveMany studies have shown that the nature of the lipid consumed in the diet significantly affects the development of inflammatory diseases. In this study, we compared the effect of diets supplemented with 15% by weight of fish oil (FO), refined olive oil (ROO), and pomace olive oil (POO) with that of a low-fat diet, 2% by weight of corn oil, considered as the basal diet (BD), on the ability to modify reactive oxidative species and proinflammatory mediator generation by stimulated murine macrophages.MethodsMice were fed the different oil-enriched diets for 8 wk. Peritoneal macrophages were isolated from these mice and subsequently stimulated. Reactive oxygen species and proinflammatory mediators were measured in the corresponding supernatants. Data were statistically treated by one-way analysis of variance and Tukey's multiple comparison post hoc test.ResultsThe ROO and POO significantly reduced the hydrogen peroxide production compared with BD, whereas FO stimulated its production. Moreover, the generation of nitric oxide was significantly prevented in all the experimental oil-enriched dietary groups. The ROO and FO groups showed significantly reduced cytokine (tumor necrosis factor-α, interleukin-1β, interleukin-6) and prostaglandin E2 production.ConclusionThese results confirm the prevention action on proinflammatory mediator generation exerted by FO and demonstrate the protective antioxidant properties not only of olive oil but also of POO. The consumption of these olive oils may help to prevent cellular oxidative stress and inflammation. 相似文献
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Filho AS Maciel BC Martín-Santos R Romano MM Crippa JA 《Primary care companion to the Journal of clinical psychiatry》2008,10(1):38-47
Objective: Although the possible relationship between panic disorder and mitral valve prolapse (MVP) attracted considerable research interest in the 1980s and 1990s, the reported prevalence of MVP in these patients has been inconsistent and widely variable. Clinical and epidemiologic studies have produced controversial data on possible association or definite causal relationship between these 2 entities. The primary objective of the present review was to summarize the current state of knowledge on the association between panic disorder and MVP, including the influence of diagnostic criteria for MVP on the controversial results.Data Sources: We searched MEDLINE, LILACS, and EMBASE databases using the keywords panic and mitral. Inclusion criteria were articles concerning the reciprocal association of MVP and panic disorder, published from the earliest dates available through December 2006.Study Selection: All relevant articles published in English, Spanish, or Portuguese and reporting original data related to the association of MVP and panic disorder were included. Forty articles fulfilling the criteria for inclusion in this review were identified.Data Synthesis: Even though the reported prevalence of MVP in panic disorder varied from 0% to 57%, a significant association between the 2 disorders was documented in 17 of the 40 studies. Such inconsistent results were due to sampling biases in case or control groups, widely different diagnostic criteria for MVP, and lack of reliability of MVP diagnosis. None of the reviewed studies used the current state-of-the-art diagnostic criteria for MVP to evaluate the volunteers. Apparently, the more elaborate the study methodology, the lower the chance to observe a significant relationship between these 2 conditions.Conclusions: Published results are insufficient to definitely establish or to exclude an association between MVP and panic disorder. If any relationship does actually exist, it could be said to be infrequent and mainly occur in subjects with minor variants of MVP. To clarify this intriguing issue, future studies should mainly focus on the observed methodological biases and particularly should use the current criteria for MVP as the standard for evaluation. 相似文献
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110.
Roiz-Santiáñez R Crespo-Facorro B Pérez-Iglesias R Pelayo-Terán JM Carrasco-Marín E Mata I Sánchez E Leyva-Cobián F Vázquez-Barquero JL 《Psychiatry research》2008,162(2):167-171
Studies of schizophrenia that combine imaging and genetic approaches attempt to map structural brain anomalies associated with genetic risk variants. The aim of the present study was to investigate whether variations in the interleukin-1 receptor antagonist (IL-1RN) were associated with structural brain characteristics of 73 minimally medicated first-episode non-affective psychotic patients. We did not find evidence for association between genetic variation in the IL-1RN gene and brain morphometry at early phases of the illness. 相似文献