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961.
962.
Zalyapin EA Bouley R Hasler U Vilardaga JP Lin HY Brown D Ausiello DA 《Kidney international》2008,74(12):1557-1567
The kidney has a cortico-medullary interstitial gradient of decreasing pH and increasing concentrations of sodium chloride and urea, but the influence of these gradients on receptor signaling is largely unknown. Here, we measured G-protein coupled receptor function in LLC-PK1 cells acutely exposed to conditions mimicking different kidney regions. Signaling through the parathyroid hormone receptor, normally expressed in the cortex, was greatly reduced at an acidic pH similar to that of the inner medulla. Parathyroid hormone receptor, tagged with green fluorescent protein, showed no ligand-induced internalization. In contrast, under both acidic and hyperosmotic conditions, vasopressin increased intracellular cAMP, and upon binding to its type 2 receptor (V2R) was internalized and degraded. Dose-displacement binding assays with selective vasopressin/oxytocin receptor ligands under inner medullary conditions indicated a shift in the V2R pharmacological profile. Oxytocin did not bind to the V2R, as it does under normal conditions and the vasopressin type 1 receptor (V1R) had reduced affinity for vasopressin compared to the V2R in low pH and high osmolality. We suggest that the cortico-medullary gradient causes a receptor-specific selectivity in ligand binding that is of functional significance to the kidney. While the gradient is important for urinary concentration, it may also play a substantial role in fine-tuning of the vasopressin response through the V2R. 相似文献
963.
Regarding curative treatment of oesophageal carcinoma, many therapeutic options could be planned. Surgery is traditionally considered as the most appropriate treatment for locoregional control and long-term survival. Because of the poor prognosis, muldisciplinary approach is necessary, including surgery, radiotherapy and chemotherapy, alone or in association. However, because of the small number of well randomised trials, the question of which treatment is the most appropriate is still under debate. In 2007, following therapeutic strategies could be drawn: surgery is the main treatment, used alone for stages I and IIa, in association with neoadjuvant chemotherapy (CT) or chemoradiation (CRT) for stages IIb. For locally advanced tumours (stage III), adenocarcinomas required neoadjuvant CT or CRT followed by surgery, whereas for squamous cell carcinomas exclusive CRT is the main treatment with following important conditions : (i) response to CRT, (ii) curative salvage surgery in case of non response after 2 cycles or persistent tumour after 4 cycles, (iii) long-term survival may be probably enhanced by adjuvant surgery in experienced centres for selected patients. 相似文献
964.
Oki Y Kantarjian HM Gharibyan V Jones D O'brien S Verstovsek S Cortes J Morris GM Garcia-Manero G Issa JP 《Cancer》2007,109(5):899-906
BACKGROUND: Resistance to imatinib is a frequent clinical problem in advanced phase chronic myelogenous leukemia (CML). A Phase II study was performed on low-dose decitabine, a DNA methyltransferase inhibitor, in combination with imatinib in patients with CML in accelerated phase (AP) and myeloid blastic phase (BP). METHODS: Patients received decitabine 15 mg/m(2) intravenously daily, 5 days a week for 2 weeks, and imatinib 600 mg orally daily. Global DNA methylation was measured by long interspersed nucleotide element (LINE) bisulfite/pyrosequencing. RESULTS: Twenty-eight patients were enrolled (25 with imatinib resistance; 18 in AP, 10 in BP). A total of 91 cycles (median, 2.5 cycles per patient) was administered. Complete hematologic responses, partial hematologic responses, and hematologic improvement were observed in 9 (32%), 1 (4%), and 2 (7%) patients. Major and minor cytogenetic responses were observed in 5 (18%) and 3 (11%) patients. The hematologic response rate was higher in patients without BCR-ABL kinase mutations (10 of 19, 53%) than in those with mutations (1 of 7, 14%). Median duration of hematologic response was 18 (range, 4 to 107+) weeks. Myelosuppression was the major adverse effect, with neutropenic fever in 9 patients (32%). LINE methylation decreased from 71.6% +/- 0.9% (mean +/- standard error of the mean) to 60.4% +/- 2.0% on Day 5, 60.5% +/- 1.8% on Day 12, and returned to 68.8% +/- 1.4% at peripheral blood recovery. A decrease in LINE methylation tended to be greater in nonresponders than in responders on Days 5 and 12. CONCLUSIONS: Combination therapy with decitabine and imatinib is well tolerated and active in advanced phase CML without BCR-ABL kinase mutations. 相似文献
965.
Kantarjian HM O'Brien S Huang X Garcia-Manero G Ravandi F Cortes J Shan J Davisson J Bueso-Ramos CE Issa JP 《Cancer》2007,109(6):1133-1137
BACKGROUND: Decitabine, a hypomethylating agent, is active and has been approved for the treatment of myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia. Intensive chemotherapy is an accepted form of therapy for patients with higher risk MDS. The comparative efficacy of these 2 forms of treatment in MDS is unknown. The objective of the current study was to compare the efficacy and toxicity profiles of decitabine and intensive chemotherapy in MDS. METHODS: The authors compared lower intensity decitabine therapy (n = 115 patients) with intensive chemotherapy (as it is used in acute myeloid leukemia [AML]) in patients with higher risk MDS. Two comparisons were made with a cohort of 376 historic patients (from 1995 to 2005): The first comparison included a subcohort of 115 patients (Group A) who matched the 115 decitabine study patients according to age, International Prognostic Scoring System, and cytogenetics; and the second comparison included the whole cohort of 376 patients without matching (Group B). A multivariate analysis was performed for outcome. RESULTS: The complete remission (CR) rate according to AML criteria was 43% with decitabine, 46% with intensive chemotherapy in Group A, and 52% with intensive chemotherapy in Group B. Compared with Group A, mortality at 6 weeks was 3% with decitabine versus 13% with intensive chemotherapy (P = .006) and, at 3 months, 7% with decitabine versus 23% with intensive chemotherapy (P = .001). Survival was better with decitabine versus intensive chemotherapy in Group A (median survival: 22 months vs 12 months; P < .001). A multivariate analysis of survival in all 491 patients who received decitabine or intensive chemotherapy (Group B) selected decitabine as an independent, favorable prognostic factor for survival (P = .006; hazard ratio, 0.74) after accounting for the independent prognostic effect of pretreatment factors. CONCLUSIONS: In this analysis, decitabine was associated with a survival advantage compared with intensive chemotherapy in patients with higher risk MDS. Future studies should evaluate prospectively the results of decitabine versus intensive chemotherapy in this setting. 相似文献
966.
967.
Accuracy of the screening physical examination to identify subclinical atherosclerosis and peripheral arterial disease in asymptomatic subjects 总被引:1,自引:0,他引:1
Cournot M Boccalon H Cambou JP Guilloux J Taraszkiewicz D Hanaire-Broutin H Chamontin B Galinier M Ferrières J 《Journal of vascular surgery》2007,46(6):1215-1221
OBJECTIVES: This study assessed the accuracy of the screening vascular physical examination for predicting asymptomatic peripheral arterial disease (PAD) or subclinical atherosclerosis in asymptomatic and apparently healthy subjects. METHODS: A standardized physical examination and a carotid and femoral ultrasonography were administered to 2736 men and women aged 20 to 90 years old, with no personal history of cardiovascular disease (CVD) and no complaint of neurologic, coronary, or lower limb symptom. We assessed the accuracy of auscultation for bruits and pulse palpation for identifying the presence of significant carotid stenosis, carotid plaque, femoral plaque, and ankle-brachial index (ABI) <0.9 at ultrasonography. RESULTS: The presence of a femoral bruit provided information on the presence of both an ABI <0.9 (positive likelihood ratio [+LR], 2.90; 95% confidence interval [CI], 1.63 to 5.16) and a femoral plaque (+LR, 3.23; 95% CI, 2.22 to 4.71), and this information was independent from the cardiovascular risk factors. The absence of both pedal pulses also provided additional information, beyond risk factors, on the presence of an ABI <0.9 (+LR, 3.57; 95% CI, 1.93 to 6.60). The presence of a carotid bruit did not affect the likelihood of carotid stenosis, plaque, or intima-media thickness above the median. CONCLUSION: Unlike carotid auscultation, pulse palpation and auscultation for femoral bruits provided valuable information on the presence of asymptomatic PAD and underlying atherosclerosis in apparently healthy subjects. 相似文献
968.
Jung B Sebbane M Chanques G Courouble P Cisse M Perrigault PF Jean-Pierre H Eledjam JJ Jaber S 《Annales fran?aises d'anesthèsie et de rèanimation》2007,26(10):844-849
Objectives
To compare the clinical outcomes and the causative pathogens of early-onset and late-onset ventilator-associated pneumonia (VAP) diagnosed by bronchoalveolar lavage (BAL).Study design
Prospective, observational, epidemiological study.Patients and methods
During a 7-years period, all first episodes of VAP were prospectively included. Diagnosis was confirmed by a BAL with a threshold of 104 cfu/ml. Late-onset pneumonia was defined if occurred after the seventh day after mechanical ventilation.Results
One hundred and thirteen VAP were studied. Fifty were early-onsets and 63 late-onsets. Thirty-four per cent of early-onset VAP and 73% of late-onset VAP were due to potential multiresistants pathogens. Pseudomonas aeruginosa was the most commonly isolated bacteria both in early-onset and late-onset VAP (16 and 39% respectively). Morbidity and mortality (29 vs 29%, ns) were not statically different between the two groups (early-onset and late-onset VAP).Conclusion
In our study, both early-onset and late-onset VAP were mainly caused by potentially multiresistants bacteria, most commonly Gram negative bacilli. Even for early VAP, clinicians should be aware about all risk factors for potentially multiresistants pathogens and not only the delay of onset of the VAP episode. 相似文献969.
Two types of circulating endothelial progenitor cells in patients receiving long term therapy by HMG-CoA reductase inhibitors 总被引:7,自引:0,他引:7
Deschaseaux F Selmani Z Falcoz PE Mersin N Meneveau N Penfornis A Kleinclauss C Chocron S Etievent JP Tiberghien P Kantelip JP Davani S 《European journal of pharmacology》2007,562(1-2):111-118
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used to decrease cholesterol synthesis and are well established to reduce vascular diseases. Recently, it has been proposed that statins mobilize endothelial progenitor cells from bone marrow during the first four weeks, which could help to prevent vascular diseases. However, in humans there are few data concerning the long term effects of statin treatment on these endothelial progenitor cells. We investigated whether endothelial progenitor cells can be detected and characterized in patients receiving long term statin therapy. Mononuclear cells from patients receiving or not receiving statin therapy were assessed for progenitor cell content by flow cytometry and were cultured in specific conditions to determine the number and the type of progenitors. Our results showed there were significantly more CD34(+), CD34(+)/CD144(+) circulating progenitor cells in the statin(pos) group than in the statin(neg) group. In culture two types of endothelial progenitor cells were detected. Early endothelial progenitor cells gave colonies at day 5 comprising elongated cells whereas late endothelial progenitor cells generated cobblestone-like colonies with strong proliferation capacities. The number of circulating early endothelial progenitor cells was significantly higher in the statin(neg) group, while only late endothelial progenitor cells were detected in the statin(pos) group. Moreover, cells from cobblestones clearly had an endothelial phenotype CD31(+), VEGF-R2(+), CD34(+), CD146(+) in contrast to cells from colonies from early endothelial progenitor cells, which were VEGF-R2(low), CD34(-). These results strongly suggest that long term statin treatment specifically maintains late endothelial progenitor cells in circulation with a CD34(+)/CD144(+) phenotype. 相似文献
970.
Percutaneous pedicle screw instrumentation for temporary internal bracing of nondisplaced bony Chance fractures 总被引:1,自引:0,他引:1
Beringer W Potts E Khairi S Mobasser JP 《Journal of spinal disorders & techniques》2007,20(3):242-247
OBJECTIVE AND IMPORTANCE: Although many patients with unstable Chance fractures can heal in an external brace, others will require internal stabilization. Short-segment minimally invasive internal bracing of a Chance fracture offers the rigidity and patient compliance of internal bracing with minimal tissue disruption. This technique has not yet been described. CLINICAL PRESENTATION: A healthy 16-year-old female and 21-year-old male sustained classic nondisplaced Chance fractures. They were both neurologically intact. TECHNIQUE: An image-guided Jamshidi needle was used to percutaneously place K-wires to direct percutaneous pedicle screws. Freehand percutaneous passing of rods to connect the pedicle screw heads on each side created a short-segment construct. CONCLUSIONS: Minimally invasive internal bracing of nondisplaced bony Chance fractures is an option for selected neurologically intact patients unable to tolerate external bracing. 相似文献