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61.
Background
Pulmonary hypertension (PH) is one of the most important comorbidities in patients undergoing hemodialysis (HD). The goal of the present work is to determine the possible etiologic factors for its occurrence.Methods
The prevalence of PH was estimated by Doppler echocardiography in a cohort of 100 patients aged 49.3 ± 13.9 years on regular HD. Mean pulmonary artery pressure was estimated from pulmonary acceleration time by Mahan’s regression equation. Pulmonary vascular resistance and pulmonary capillary wedge pressure were calculated. We focused on the effect of HD on left and right ventricle diastolic and systolic function. Right ventricle systolic function was assessed by tricuspid annular systolic excursion and pulsed Doppler myocardial performance index. Since impaired endothelial function was postulated as an underlying cause of PH, we studied the effects of HD on brachial artery endothelial function.Results
The current study found that pulmonary hypertension was prevalent in 70% of patients on dialysis. Left atrium diameter, left ventricle mass indexed to body surface area, and mitral E/E′ were increased in the dialysis group (4.4 ± 0.2 cm, 126.5 ± 24.6 g/m2, and 16.9 ± 4.4, respectively, p < 0.001 for all). Pulmonary artery systolic pressure was positively correlated to duration of dialysis and negatively correlated to glomerular filtration rate (p < 0.001 and r = −0.991). Pulmonary vascular resistance was significantly increased in dialysis patients (1.9 ± 0.2 Wood units vs. 1.2 Wood units in controls, p < 0.001). Endothelial dysfunction, defined as brachial artery flow mediated dilatation <6%, was found in 46% of dialysis group.Conclusion
Increased pulmonary artery systolic pressure in the HD population could be attributed to left atrium dilatation and left ventricle diastolic dysfunction. Pulmonary vascular resistance was significantly increased in dialysis group. This might be explained by impaired endothelial nitric oxide synthesis that not only caused systemic vasoconstriction but also affected the pulmonary vasculature. 相似文献62.
63.
El-Tahan MR Al Dossary ND El Emam H Diab DG Al'Saflan A Zien H Al Ahmadey M Deria A 《Surgical endoscopy》2012,26(2):391-397
Background
Hypocapnia before and during carbon dioxide (CO2) insufflation for laparoscopic cholecystectomy may reduce the adverse hemodynamic responses. 相似文献64.
65.
Mohsin Shah Jean H. Tayar Noha Abdel-Wahab Maria E. Suarez-Almazor 《Seminars in arthritis and rheumatism》2019,48(4):736-740
Objectives
Immune checkpoint inhibitors (ICIs) can successfully treat cancer, but their use can be hindered by serious immune-related adverse events. We report six patients receiving ICIs who presented with de novo myositis.Methods
We identified patients with myositis who were receiving ICIs between January 2004 and September 2016 at The University of Texas MD Anderson Cancer Center.Results
Six patients developed de novo myositis. The mean age was 64.3 years and five patients were male. Cancer types included melanoma, urothelial carcinoma, renal cell carcinoma, and prostate cancer. ICI regimens included single-agent ipilimumab (n = 1), pembrolizumab (n = 1), or atezolizumab (n = 1); nivolumab and ipilimumab (n = 3). The median time to development of de novo myositis from first infusion was 5.4 weeks (range: 2.1–17.1 weeks). All patients with myositis had elevated levels of creatinine kinase, ranging from 514 to 13,710 U/L. Two of them developed rhabdomyolysis, one with concurrent myocarditis. Five patients were treated with 1–2 mg/kg corticosteroids, with variable response rates; one patient received nonsteroidal anti-inflammatory drugs. Two patients with myositis died as a result of cancer progression.Conclusion
We found several occurrences of de novo myositis following ICI therapy. These preliminary data suggest that myositis can occur early after onset of ICI therapy with serious adverse outcomes. 相似文献66.
67.
IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients
Mostafa K El Awady Noha G Bader El Din Ashraf Tabll Yaser El Hosary Ashraf O Abdel Aziz Hesham El Khayat Mohsen Salama Tawfeek H Abdelhafez 《World journal of gastroenterology : WJG》2013,19(2):290-298
AIM:To test whether the status of positive cytomegalovirus(CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers.METHODS:This study included 166 chronic hepatitis C(CHC) patients who received combined interferon and ribavirin therapy for 48 wk,84 spontaneous hepatitis C virus(HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA,and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls.Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism(SNP) and CMV DNA detection.A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer.Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism(RFLP) genotyping.The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction.The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed.RESULTS:Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response(SVR) while the genotypes C/T and TT were associated with lower SVR rates,50% and 48%,respectively.SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations.Genotype CC was associated with the response to interferon(P = 0.025).Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity.The majority of spontaneously cleared subjects(86%) were C/C,confirming its protective role.The C/T allele was present in 71% of CHC patients compared with 38% of controls,so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response.CMV reactivation occurred in 40% of CHC patients.Co-infection with CMV seriously diminished the response to inter 相似文献
68.
Jill M. Butterfield Bruce A. Mueller Nimish Patel Katie E. Cardone Darren W. Grabe Noha N. Salama Thomas P. Lodise 《Antimicrobial agents and chemotherapy》2013,57(2):864-872
While the pharmacokinetic (PK) properties of daptomycin in hemodialysis (HD) patients have been evaluated previously by three groups, resultant dosing recommendations have varied. To address this clinical conundrum, this study combined concentration-time data from these PK evaluations and derived uniform dosing recommendations among patients on HD receiving daptomycin. A two-compartment model with separate HD and non-HD clearance terms was fit to the PK data from these studies by using BigNPAG. Embedded with PK parameters from the population PK analysis, 5,000-subject Monte Carlo simulations (MCS) were performed to identify HD dosing schemes that provided efficacy (cumulative and daily area under the concentration-time curve [AUC] values) and toxicity (trough concentrations of ≥24.3 mg/liter) profiles comparable to those from simulations employing the daptomycin PK model derived from the Staphylococcus aureus bacteremia–infective endocarditis (SAB-IE) study. Separate HD dosing schemes were sought for the two weekly interdialytic periods (48 and 72 h). For the 48-h interdialytic period, intra- and post-HD dosing provided the most isometric cumulative and daily AUCs. For the 72-h interdialytic period, all HD dosing schemes provided noncumulative AUC values from 48 to 72 h (AUC48–72) that were <50% of the SAB-IE AUC48–72 values. Increasing the parent dose by 50% intra- or post-HD provided comparable AUC48–72 values, while maintaining acceptable trough concentration (Cmin) values. When efficacy and toxicity profiles were evaluated for each individual study, higher probabilities for Cmin reaching ≥24.3 mg/liter were observed in one of the three studies. Given the high probability of Cmin being ≥24.3 mg/liter in one of the three studies, more intensive creatine phosphokinase (CPK) monitoring may be warranted in HD patients receiving daptomycin. 相似文献
69.
70.
To date, research on the effect of single nucleotide polymorphisms (SNPs) on P-glycoprotein (P-gp) expression and functionality has rendered inconsistent results. This study systematically evaluates the impact of MDR1 haplotypes (1236/2677, 1236/3435, 2677/3435, 1236/2677/3435) on P-gp functionality compared to individual SNPs (1236, 2677, and 3435) in validated stable recombinant epithelial cells. Recombinant LLC-PK1 cells expressing MDR1wt or its variants were developed and validated for this purpose. Intracellular accumulation and time-dependant efflux of a P-gp substrate, Rhodamine 123 (R123, 5 microM) were evaluated in control and recombinant cells. Additionally, the transepithelial transport of R123 (1 microM) and Vinca alkaloids (5 microM) was evaluated. Except for MDR1(2677T) and MDR1(1236T/2677T/3435T), cells expressing MDR1 variants displayed intermediate R123 intracellular accumulation (1.5-2-fold higher) and lower effluxed R123 (10-20% vs. 52%) compared to those expressing MDR1wt. Efflux ratios across MDR1wt expressing cells were significantly larger for R123 (3.95+/-1.1), Vinblastine (3.75+/-0.26), and Vincristine (2.8+/-0.29). Recombinant cells expressing MDR1 variants displayed 0%-22.7% P-gp activity (approximately 80%-100% efflux loss). Results suggest that MDR1 polymorphisms at the 1236, 2677, and/or 3435 positions significantly minimize P-gp functionality in vitro, the extent of which appears to be substrate dependant. 相似文献