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61.
Antonio Jimeno Cristina Grávalos Pilar Escudero Isabel Sevilla M. Eugenia Vega-Villegas Vicente Alonso Ignacio Juez Rocío García-Carbonero Humberto Bovio Ramón Colomer Hernán Cortés-Funes 《Clinical & translational oncology》2008,10(1):52-57
Objective The objectives of this phase I/II study were to determine the maximum tolerated dose (MTD), characterise the principal toxicities
in the phase I part and assess the efficacy in the phase II part of gefitinib, an oral selective inhibitor of the epidermal
growth factor receptor, in combination with capecitabine in patients with advanced colorectal cancer (CRC).
Methods and patients Patients with advanced CRC were treated with gefitinib administered daily for 21 days and capecitabine administered twice
daily for 14 days of a 21-day cycle. The dose levels of gefitinib (mg) and capecitabine (mg/m2 bid) assessed were 250/1000 and 250/ 1250. An expanded cohort was enrolled at the MTD to better characterise toxicity and
efficacy. A total of 32 previously treated patients were accrued. In the phase I part 10 subjects were treated, with one dose-limiting
toxicity. Overall 26 patients were treated at the MTD of the combination, which was gefitinib 250 mg/day and capecitabine
1250 mg/m2 twice daily.
Results The most frequent treatment-related adverse events included asthenia, diarrhoea, nausea, rash and anorexia. The incidence
profile was very similar in phases I and II. No objective responses were documented but 53% of the patients achieved stable
disease as best response to therapy.
Conclusions Capecitabine 1250 mg/m2 twice daily 14 of 21 days and gefitinib at 250 mg/day can be safely administered in combination. The combination is relatively
well tolerated. There were no objective responses, although an interesting stabilisation rate was documented, in previously
treated advanced CRC patients. 相似文献
62.
Paulo A Martins S Branco P Dias T Borges C Rodrigues AI Costa Mdo C Teixeira A Mota-Filipe H 《Phytotherapy research : PTR》2008,22(4):539-543
The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin. 相似文献
63.
64.
Isabel Santillán Palencia Letizia Benassi StradaLaura Blasco Gastón Inma Rincón RicoteRomán Curiel Rodado Antonio González González 《Progresos de Obstetricia y Ginecología》2008
Objectives
To evaluate maternal and fetal outcomes of multiple pregnancy according to route of delivery.Material and methods
We performed a retrospective study of all twin deliveries in the previous 5 years and evaluated the route of delivery, especially in the final year. The information was recorded with Microsoft EXCEL and was analyzed with the statistical program SPSS 12.0 for Windows.Results
The mean gestational age was 35.3 weeks. Route of delivery was through cesarean section in 59.8%. The mean interval between twins was 7.82 minutes when the first twin was delivered vaginally. Neonatal morbidity was found in 49%, and was higher in the second twin and in preterm deliveries.Conclusions
Multiple pregnancies are associated with a large number of maternal and perinatal complications, as well as with a greater number of cesarean sections. Consequently, correct intrapartum management is required to reduce neonatal morbility as far as possible. 相似文献65.
Cristina Dopazo Itxarone Bilbao Sonia García Concepcin GmezGavara Mireia Caralt Isabel CamposVarela Lluis Castells Ernest Hidalgo Francisco Moreso Bruno Montoro Ramn Charco 《CTS Clinical and Translational Science》2022,15(6):1544
Tacrolimus (TAC) is a dose‐dependent immunosuppressor with considerable intrapatient variability (IPV) in its pharmacokinetics. The aim of this work is to ascertain the association between TAC IPV at 6 months after liver transplantation (LT) and patient outcome. This single‐center cohort study retrospectively analyzed adult patients who underwent transplantation from 2015 to 2019 who survived the first 6 months with a functioning graft. The primary end point was the patient’s probability of death and the secondary outcome was the loss of renal function between month 6 and the last follow‐up. TAC IPV was estimated by calculating the coefficient of variation (CV) of the dose‐corrected concentration (C0/D) between the third and sixth months post‐LT. Of the 140 patients who underwent LT included in the study, the low‐variability group (C0/D CV < 27%) comprised 105 patients and the high‐variability group (C0/D CV ≥ 27%) 35 patients. One‐, 3‐, and 5‐year patient survival rates were 100%, 82%, and 72% in the high‐variability group versus 100%, 97%, and 93% in the low‐variability group, respectively (p = 0.005). Moreover, significant impaired renal function was observed in the high‐variability group at 1 year (69 ± 16 ml/min/1.73 m2 vs. 78 ± 16 ml/min/1.73 m2, p = 0.004) and at 2 years post‐LT (69 ± 17 ml/min/1.73 m2 vs. 77 ± 15 ml/min/1.73 m2, p = 0.03). High C0/D CV 3–6 months remained independently associated with worse survival (hazard ratio = 3.57, 95% CI = 1.32–9.67, p = 0.012) and loss of renal function (odds ratio = 3.47, 95% CI = 1.30–9.20, p = 0.01). Therefore, high IPV between the third and sixth months appears to be an early and independent predictor of patients with poorer liver transplant outcomes.
Abbreviations
- BPAR
- Biopsy proven acute rejection
- BMI
- Body mass index
- CKD‐EPI
- chronic kidney disease epidemiology collaboration
- CV
- coefficient of variation
- C0/D
- dose‐corrected concentration
- CMV
- cytomegalovirus
- eGFR
- estimated glomerular filtration rate
- HR
- hazard ratio
- HCC
- hepatocellular carcinoma
- ICU
- intensive care unit
- IPV
- intrapatient variability
- i.v.
- intravenously
- LC–MS/MS
- liquid chromatography‐ tandem mass spectrometry
- LT
- liver transplantation
- MELD
- model for end‐stage liver disease
- MMF
- mycophenolate mofetil
- NASH
- Non‐Alcoholic Steatohepatitis
- OR
- odds ratio
- PCR
- polymerase chain reaction
- SD
- Standard Deviation
- TAC
- tacrolimus
- 3–6 M
- three–six months
- WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
- WHAT QUESTION DID THIS STUDY ADDRESS?
- WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
- HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
66.
Sónia Gonçalves Ana Isabel Vieira Bárbara César Machado Renata Costa Joana Pinheiro Eva Conceiçao 《Children's Health Care》2013,42(3):301-313
This study sought to determine the frequency of possible cases of avoidant/restrictive food intake disorder (ARFID) in a Portuguese sample of school-aged children and to assess the associations with child’s internalizing problems, BMI z-score and body dissatisfaction, and parents’ eating habits, attitudes and practices. We assessed 330 children through child’s and parents’measures. Fifty-one (15.5%) children were possible cases of ARFID based on their symptom’s presentation. There were no association between sex and possible cases of ARFID, and no significant differences between possible cases of ARFID and nonpossible cases of ARFID regarding age. Lower BMI z-score and anxiety/depression were associated with possible cases of ARFID. 相似文献
67.
Amy C. Morrison Robert C. Reiner Jr. William H. Elson Helvio Astete Carolina Guevara Clara del Aguila Isabel Bazan Crystyan Siles Patricia Barrera Anna B. Kawiecki Christopher M. Barker Gissella M. Vasquez Karin Escobedo-Vargas Carmen Flores-Mendoza Alfredo A. Huaman Mariana Leguia Maria E. Silva Sarah A. Jenkins Wesley R. Campbell Eugenio J. Abente Robert D. Hontz Valerie A. Paz-Soldan John P. Grieco Neil F. Lobo Thomas W. Scott Nicole L. Achee 《Proceedings of the National Academy of Sciences of the United States of America》2022,119(26)
Over half the world’s population is at risk for viruses transmitted by Aedes mosquitoes, such as dengue and Zika. The primary vector, Aedes aegypti, thrives in urban environments. Despite decades of effort, cases and geographic range of Aedes-borne viruses (ABVs) continue to expand. Rigorously proven vector control interventions that measure protective efficacy against ABV diseases are limited to Wolbachia in a single trial in Indonesia and do not include any chemical intervention. Spatial repellents, a new option for efficient deployment, are designed to decrease human exposure to ABVs by releasing active ingredients into the air that disrupt mosquito–human contact. A parallel, cluster-randomized controlled trial was conducted in Iquitos, Peru, to quantify the impact of a transfluthrin-based spatial repellent on human ABV infection. From 2,907 households across 26 clusters (13 per arm), 1,578 participants were assessed for seroconversion (primary endpoint) by survival analysis. Incidence of acute disease was calculated among 16,683 participants (secondary endpoint). Adult mosquito collections were conducted to compare Ae. aegypti abundance, blood-fed rate, and parity status through mixed-effect difference-in-difference analyses. The spatial repellent significantly reduced ABV infection by 34.1% (one-sided 95% CI lower limit, 6.9%; one-sided P value = 0.0236, z = 1.98). Aedes aegypti abundance and blood-fed rates were significantly reduced by 28.6 (95% CI 24.1%, ∞); z = −9.11) and 12.4% (95% CI 4.2%, ∞); z = −2.43), respectively. Our trial provides conclusive statistical evidence from an appropriately powered, preplanned cluster-randomized controlled clinical trial of the impact of a chemical intervention, in this case a spatial repellent, to reduce the risk of ABV transmission compared to a placebo.Aedes-borne viral diseases (ABVDs) [e.g., dengue (DENV), chikungunya, Zika (ZIKV), and yellow fever] are devastating, expanding global public health threats that disproportionally affect low- and middle-income countries. DENV, one of the most rapidly increasing vector-borne infectious diseases, results in ∼400 million infections each year (1, 2), with 4 billion people at risk for infection annually (3). Currently, the primary means for ABVD prevention is controlling the primary mosquito vector, Aedes aegypti. Existing vector control interventions, however, have failed to prevent ABV transmission and epidemics (4–6).There is an urgent need to develop evidence-based guidance for the use of new and existing ABV vector control tools. The evidence base for vector control against ABVs is weak, despite considerable government investments in World Health Organization (WHO)-recommended control of larval habitats (larviciding, container removal) and ultra-low-volume insecticide spraying (4, 5, 7–9). These strategies continue to be implemented despite the lack of rigorously generated data from controlled clinical trials demonstrating they reduce ABV infection or disease (6). The only ABV intervention with a proven epidemiological impact in a cluster-randomized control trial (cRCT) assessed community mobilization to reduce mosquito larval habitats (10). A recent test-negative trial with Wolbachia-infected mosquitoes reported a significant reduction of DENV illness in Indonesia (11).Spatial repellents (SRs) are devices that contain volatile active ingredients that disperse in air. The active ingredients can repel mosquitoes from entering a treated space, inhibit attraction to human host cues, or disrupt mosquito biting and blood-feeding behavior and, thus, interfere with mosquito–human contact (12–14). Any of these outcomes reduce the probability of pathogen transmission. Pyrethroid-based SRs have shown efficacy in reducing malaria infections in China (15) and Indonesia (16). There have, however, been no clinical trials evaluating the protective efficacy (PE) of SRs against ABV infection or disease.To generate evidence for public health consideration, we conducted a double-blinded, parallel cRCT to demonstrate and quantify the PE of a transfluthrin-based SR to reduce ABV infection incidence over 2 y in a human cohort in Iquitos, Peru. 相似文献
68.
69.
70.
Malignant Gastric and Duodenal Stenosis: Palliation by Peroral Implantation of a Self-Expanding Metallic Stent 总被引:11,自引:0,他引:11
Isabel T. Pinto 《Cardiovascular and interventional radiology》1997,20(6):431-434
Purpose: To assess the use of self-expanding metallic stents in patients with inoperable malignant antrum-pylorus-duodenal obstruction.
Methods: Six patients underwent implantation of a Wallstent self-expanding metallic endoprosthesis (20 mm in five patients and 16
mm in one). In five patients a catheter (Berenstein) was introduced perorally into the stomach. A guidewire (Terumo) was introduced
through the catheter and advanced through the antrum-pylorus-duodenal stenosis. The guidewire was removed and a 260-cm-long,
0.035″ superstiff guide (Amplatz) was introduced. After the catheter was removed the stent assembly was introduced. In the
last patient the stent was implanted through a percutaneous gastrostomy.
Results: Treatment of inoperable gastric outlet obstruction caused by tumor compression is difficult and unsatisfactory. Peroral implantation
of self-expanding metallic stents resulted in successful palliative therapy of antrum-pylorus-duodenal stenosis in six patients
in whom surgery was not possible because of advanced disease and poor general condition. On average, patients were able to
eat during 41 days. One patient is tolerating oral intake at 3 months.
Conclusion: Implantation of stents resulted in palliative relief of malignant antrum-pylorus-duodenal obstructions.
Received: 0/00/00/Accepted: 0/00/00 相似文献