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1.
Bancha Satirapoj Surat Tassanasorn Mongkon Charoenpitakchai Ouppatham Supasyndh 《PloS one》2015,10(4)
Background
Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.Methods
Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114), microalbuminuria (n=100) and macroalbuminuria (n=114). The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.Results
Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77) ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29) ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19) ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63) ng/mgCr] (P<0.01).Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86), 0.99 (95%CI, 0.98 to 1.00) and 0.95 (95%CI, 0.91 to 0.98), respectively).Conclusion
The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury. 相似文献2.
Krzysztof Wanic Bozena Krolewski Wenjun Ju Grzegorz Placha Monika A. Niewczas William Walker James H. Warram Matthias Kretzler Andrzej S. Krolewski 《PloS one》2013,8(3)
Background
In patients with Type 1 Diabetes (T1D) who develop microalbuminuria, progressive decline in glomerular filtration rate (GFR) may be initiated by leakage into the urine of toxic proteins (txUPs). This study tested this hypothesis.Methods
After archiving baseline urine, we followed T1D patients with microalbuminuria for 8–12 years to distinguish those in whom GFR declined (Decliners) and those in whom it remained stable (Non-decliners). Human proximal tubular cells (HK-2 cells) were grown in serum-free medium enriched with pooled urines from Decliners or Non-decliners. We determined genome-wide expression profiles in extracted mRNA.Results
The two pooled urines induced differential expression of 312 genes. In terms of gene ontology, molecular functions of the 119 up-regulated genes were enriched for protein binding and peptidase inhibitor activities. Their biologic processes were enriched for defense response, responses to other organisms, regulation of cellular processes, or response to stress or stimulus, and programmed cell death. The 195 down-regulated genes were disproportionately represented in molecular functions of cation binding, hydrolase activity, and DNA binding. They were disproportionately represented in biological processes for regulation of metabolic processes, nucleic acid metabolic processes, cellular response to stress and macromolecule biosynthesis. The set of up-regulated genes in HK-2 cells overlaps significantly with sets of over-expressed genes in tubular and interstitial compartments of kidney biopsies from patients with advanced DN (33 genes in one study and 25 in the other compared with 10.3 expected by chance, p<10−9 and p<10−4, respectively). The overlap included genes encoding chemokines and cytokines. Overlap of down-regulated genes was no more than expected by chance.Conclusions
Molecular processes in tubules and interstitium seen in advanced diabetic nephropathy can be induced in vitro by exposure to urine from patients with minimal microalbuminuria who subsequently developed progressive renal function decline, presumably due to putative txUPs. 相似文献3.
van der Tol A Van Biesen W Verbeke F De Groote G Vermeiren F Eeckhaut K Vanholder R 《PloS one》2010,5(10):e13328
Background
There remains debate about the screening strategies for albuminuria. This study evaluated whether a screening strategy in an apparently healthy population based on basic clinical and biochemical parameters could be more effective than a strategy where screening for albuminuria is performed unselectively.Methodology/Principal Findings
The Unreferred Renal Insufficiency (URI) Study is a cross-sectional study on the prevalence of metabolic risk factors in Belgian workers, volunteering to be screened during a routine yearly occupational check-up. Subjects (n = 295) with treated hypertension, known diabetes, treated dyslipidaemia, cardiovascular and renal disease were excluded. Among 1,191 apparently healthy subjects, 23% had unknown hypertension, 13% had impaired glucose tolerance, 15.4% had normoalbuminuria, 4.2% had microalbuminuria and 0.4% had macroalbuminuria. Subjects with resting heart rate ≥85 bpm, plasma glucose ≥5.6 mmol/L and blood pressure ≥140/90 mmHg were associated with albuminuria of any degree. A strategy where only subjects with at least one of these risk factors (n = 431) were screened for albuminuria, would identify all subjects with macroalbuminuria (5/5), 64% of those with microalbuminuria (32/50), and less than half of those with normoalbuminuria (81/183). An alternative strategy whereby subjects were first screened for presence of albuminuria, and additional cardiovascular risk factors were only measured in subjects positive for albuminuria (n = 238), would identify only 27% (118/431) of the subjects with additional and potentially modifiable cardiovascular risk factors. On the other hand, half of the subjects in this study with albuminuria (120/238, of which 102 had normoalbuminuria), had no additional cardiovascular risk factor at all.Conclusions
Screening an apparently healthy population directly for albuminuria will result in a high percentage of false positives, mostly measured in the normal range. Screening for microalbuminuria and macroalbuminuria based on presence of additional, potentially modifiable risk factors appears to be more beneficial. Trial registration 2006 NCT00365911相似文献4.
Yan Huang Haoyong Yu Junxi Lu Kaifeng Guo Lei Zhang Yuqian Bao Haibing Chen Weiping Jia 《PloS one》2012,7(11)
Background
Low vitamin D levels can be associated with albuminuria, and vitamin D analogs are effective anti-proteinuric agents. The aim of this study was to investigate differences in vitamin D levels between those with micro- and those with macroalbuminuria, and to determine whether low dose cholecalciferol increases vitamin D levels and ameliorates albuminuria.Methods
Two studies were performed in which 25-OH vitamin D3 (25(OH)D3) concentrations were determined by electrochemiluminescence immunoassay: 1) a cross-sectional study of patients with type 2 diabetes mellitus (T2DM) (n = 481) and healthy controls (n = 78); and 2) a longitudinal study of T2DM patients with albuminuria treated with conventional doses, 800 IU, of cholecalciferol for 6 months (n = 22), and a control group (n = 24).Results
1) Cross-sectional study: Compared to controls and T2DM patients with normoalbuminuria, serum 25(OH)D3 concentrations were significantly lower in patients with macro-albuminuria, but not in those with micro-albuminuria. Serum 25(OH)D3 levels were independently correlated with microalbuminuria. 2) Longitudinal study: Cholecalciferol significantly decreased microalbuminuria in the early stages of treatment, in conjunction with an increase in serum 25(OH)D3 levels.Conclusions
Low vitamin D levels are common in type 2 diabetic patients with albuminuria, particularly in patients with macroalbuminuria, but not in those with microalbuminuria. Conventional doses of cholecalciferol may have antiproteinuric effects on Chinese type 2 diabetic patients with nephropathy. 相似文献5.
Chien-Yi Hsu Po-Hsun Huang Chia-Hung Chiang Hsin-Bang Leu Chin-Chou Huang Jaw-Wen Chen Shing-Jong Lin 《PloS one》2013,8(7)
Background
Recent research indicates hypertensive patients with microalbuminuria have decreased endothelial progenitor cells (EPCs) and increased levels of endothelial apoptotic microparticles (EMP). However, whether these changes are related to a subsequent decline in glomerular filtration rate (GFR) remains unclear.Methods and Results
We enrolled totally 100 hypertensive out-patients with eGFR ≥30 mL/min/1.73 m2. The mean annual rate of GFR decline (△GFR/y) was −1.49±3.26 mL/min/1.73 m2 per year during the follow-up period (34±6 months). Flow cytometry was used to assess circulating EPC (CD34+/KDR+) and EMP levels (CD31+/annexin V+) in peripheral blood. The △GFR/y was correlated with the EMP to EPC ratio (r = −0.465, p<0.001), microalbuminuria (r = −0.329, p = 0.001), and the Framingham risk score (r = −0.245, p = 0.013). When we divided the patients into 4 groups according to the EMP to EPC ratio, there was an association between the EMP to EPC ratio and the ΔGFR/y (mean ΔGFR/y: 0.08±3.04 vs. −0.50±2.84 vs. −1.25±2.49 vs. −4.42±2.82, p<0.001). Multivariate analysis indicated that increased EMP to EPC ratio is an independent predictor of ΔeGFR/y.Conclusions
An increased circulating EMP to EPC ratio is associated with subsequent decline in GFR in hypertensive patients, which suggests endothelial damage with reduced vascular repair capacity may contribute to further deterioration of renal function in patients with hypertension. 相似文献6.
Frits A. Wijburg Bernard Bénichou Daniel G. Bichet Lorne A. Clarke Gabriela Dostalova Alejandro Fainboim Andreas Fellgiebel Cassiano Forcelini Kristina An Haack Robert J. Hopkin Michael Mauer Behzad Najafian C. Ronald Scott Suma P. Shankar Beth L. Thurberg Camilla T?ndel Anna Tylki-Szymańska Uma Ramaswami 《PloS one》2015,10(5)
Trial Design
This analysis characterizes the degree of early organ involvement in a cohort of oligo-symptomatic untreated young patients with Fabry disease enrolled in an ongoing randomized, open-label, parallel-group, phase 3B clinical trial.Methods
Males aged 5–18 years with complete α-galactosidase A deficiency, without symptoms of major organ damage, were enrolled in a phase 3B trial evaluating two doses of agalsidase beta. Baseline disease characteristics of 31 eligible patients (median age 12 years) were studied, including cellular globotriaosylceramide (GL-3) accumulation in skin (n = 31) and kidney biopsy (n = 6; median age 15 years; range 13–17 years), renal function, and glycolipid levels (plasma, urine).Results
Plasma and urinary GL-3 levels were abnormal in 25 of 30 and 31 of 31 patients, respectively. Plasma lyso-GL-3 was elevated in all patients. GL-3 accumulation was documented in superficial skin capillary endothelial cells (23/31 patients) and deep vessel endothelial cells (23/29 patients). The mean glomerular filtration rate (GFR), measured by plasma disappearance of iohexol, was 118.1 mL/min/1.73 m2 (range 90.4–161.0 mL/min/1.73 m2) and the median urinary albumin/creatinine ratio was 10 mg/g (range 4.0–27.0 mg/g). On electron microscopy, renal biopsy revealed GL-3 accumulation in all glomerular cell types (podocytes and parietal, endothelial, and mesangial cells), as well as in peritubular capillary and non-capillary endothelial, interstitial, vascular smooth muscle, and distal tubules/collecting duct cells. Lesions indicative of early Fabry arteriopathy and segmental effacement of podocyte foot processes were found in all 6 patients.Conclusions
These data reveal that in this small cohort of children with Fabry disease, histological evidence of GL-3 accumulation, and cellular and vascular injury are present in renal tissues at very early stages of the disease, and are noted before onset of microalbuminuria and development of clinically significant renal events (e.g. reduced GFR). These data give additional support to the consideration of early initiation of enzyme replacement therapy, potentially improving long-term outcome.Trial Registration
ClinicalTrials.gov NCT00701415 相似文献7.
Tadashi Toyama Kengo Furuichi Toshiharu Ninomiya Miho Shimizu Akinori Hara Yasunori Iwata Shuichi Kaneko Takashi Wada 《PloS one》2013,8(8)
Background
Precise effects of albuminuria and low estimated glomerular filtration rate (eGFR) on cardiovascular mortality, all-cause mortality, and renal events in diabetic patients are uncertain.Materials and Methods
A systematic review was conducted of the literature through MEDLINE, EMBASE, and CINHAL from 1950 to December 2010. Cohort studies of diabetic patients providing adjusted relative risk (RR) of albuminuria and eGFR for risks of cardiovascular mortality, all-cause mortality, and renal events were selected. Two reviewers screened abstracts and full papers of each study using standardized protocol.Results
We identified 31 studies fulfilling the criteria from 6546 abstracts. With regard to the risk of cardiovascular mortality, microalbuminuria (RR 1.76, 95%CI 1.38–2.25) and macroalbuminuria (RR 2.96 95%CI 2.44–3.60) were significant risk factors compared to normoalbuminuria. The same trends were seen in microalbuminuria (RR 1.60, 95%CI 1.42–1.81), and macroalbuminuria (RR 2.64, 95%CI 2.13–3.27) for the risk of all-cause mortality, and also in microalbuminuria (RR 3.21, 95%CI 2.05–5.02) and macroalbuminuria (RR 11.63, 95%CI 5.68–23.83) for the risk of renal events. The magnitudes of relative risks associated with low eGFR along with albuminuria were almost equal to multiplying each risk rate of low eGFR and albuminuria. No significant factors were found by investigating potential sources of heterogeneity using subgroup analysis.Conclusions
High albuminuria and low eGFR are relevant risk factors in diabetic patients. Albuminuria and low eGFR may be independent of each other. To evaluate the effects of low eGFR, intervention, or race, appropriately designed studies are needed. 相似文献8.
Background
Sonic hedgehog (Shh) signaling regulates cell growth during embryonic development, tissue homeostasis and tumorigenesis. Concentration-dependent cellular responses to secreted Shh protein are essential for tissue patterning. Shh ligand is covalently modified by two lipid moieties, cholesterol and palmitate, and their hydrophobic properties are known to govern the cellular release and formation of soluble multimeric Shh complexes. However, the influences of the lipid moieties on cellular reception and signal response are not well understood.Methodology/Principal Findings
We analyzed fully lipidated Shh and mutant forms to eliminate one or both adducts in NIH3T3 mouse embryonic fibroblasts. Quantitative measurements of recombinant Shh protein concentration, cellular localization, and signaling potency were integrated to determine the contributions of each lipid adduct on ligand cellular localization and signaling potency. We demonstrate that lipid modification is required for cell reception, that either adduct is sufficient to confer cellular association, that the cholesterol adduct anchors ligand to the plasma membrane and that the palmitate adduct augments ligand internalization. We further show that signaling potency correlates directly with cellular concentration of Shh ligand.Conclusions/Significance
The findings of this study demonstrate that lipid modification of Shh determines cell concentration and potency, revealing complementary functions of hydrophobic modification in morphogen signaling by attenuating cellular release and augmenting reception of Shh protein in target tissues. 相似文献9.
Rafael Medina-Navarro Itzia Corona-Candelas Saúl Barajas-González Margarita Díaz-Flores Genoveva Durán-Reyes 《PloS one》2014,9(9)
Background
A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage.Methods/Principal Findings
Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = –0.83, p<0.0001). Age, creatinine, thiol groups, and antioxidant capacity were also significantly related to the GFR decline (R = –0.47, p<0.001; R = –0.68, p<0.0001; R = 0.44, p<0.001; and R = 0.72, p<0.0001).Conclusion/Significance
The response of human albumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy. 相似文献10.
Eleonora Riccio Mauro Cataldi Maristella Minco Gennaro Argentino Roberta Russo Stefania Brancaccio Andrea Memoli Lucia Grumetto Loredana Postiglione Bruna Guida Bruno Memoli 《PloS one》2014,9(4)
Introduction
Hemodialysis (HD) and hemodiafiltration clear only with a low efficiency the plasma from interleukin-6 and p-cresol, two protein-bound uremic toxins associated with high cardiovascular risk in end stage renal disease. HFR Supra is a double-chamber hemodiafiltration system in which the ultrafiltrate returns to the patient after its regeneration through a resin cartridge that binds hydrophobic and protein-bound solutes. In the present study, we evaluated whether the HFR cartridge can also bind total p-cresol and IL-6 and remove them from the ultrafiltrate.Methods
We compared the levels of IL-6 and p-cresol in ultrafiltrate samples collected at the inlet (UFin) and at the outlet (UFout) of the cartridge at the start or at the end of a 240 min HFR session in 12 inflamed chronic HD patients. The pro-inflammatory activity of the ultrafiltrate samples was also determined by evaluating the changes that they induced in IL-6 mRNA expression and protein release in peripheral blood mononuclear cells from 12 healthy volunteers. IL-6 and p-cresol circulating levels were also assessed in peripheral plasma blood samples collected before and after HFR and, for comparison, a control HD.Results
p-Cresol and IL-6 were lower in UFout than in UFin both at the start and at the end of the HFR session, suggesting that they were retained by the cartridge. IL-6 mRNA expression and release were lower in PBMC incubated with UFout collected at the end than with UFin collected at the start of HFR, suggesting that passage through the cartridge reduced UF pro-inflammatory activity. Plasma total p-cresol decreased by about 53% after HFR, and 37% after HD. IL-6 circulating values were unmodified by either these dialysis procedures.Conclusions
This study shows that the HFR-Supra cartridge retains total p-cresol and IL-6 in the ultrafiltrate and lowers plasma total p cresol but not IL-6 levels.Trial Registration
ClinicalTrials.gov NCT01865773相似文献11.
Objective
To establish a simple two-compartment model for glomerular filtration rate (GFR) and renal plasma flow (RPF) estimations by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).Materials and Methods
A total of eight New Zealand white rabbits were included in DCE-MRI. The two-compartment model was modified with the impulse residue function in this study. First, the reliability of GFR measurement of the proposed model was compared with other published models in Monte Carlo simulation at different noise levels. Then, functional parameters were estimated in six healthy rabbits to test the feasibility of the new model. Moreover, in order to investigate its validity of GFR estimation, two rabbits underwent acute ischemia surgical procedure in unilateral kidney before DCE-MRI, and pixel-wise measurements were implemented to detect the cortical GFR alterations between normal and abnormal kidneys.Results
The lowest variability of GFR and RPF measurements were found in the proposed model in the comparison. Mean GFR was 3.03±1.1 ml/min and mean RPF was 2.64±0.5 ml/g/min in normal animals, which were in good agreement with the published values. Moreover, large GFR decline was found in dysfunction kidneys comparing to the contralateral control group.Conclusion
Results in our study demonstrate that measurement of renal kinetic parameters based on the proposed model is feasible and it has the ability to discriminate GFR changes in healthy and diseased kidneys. 相似文献12.
Background
Protein histidine phosphatase (PHP) is an enzyme which removes phosphate groups from histidine residues. It was described for vertebrates in the year 2002. The recombinant human 16 kDa protein forms multimeric complexes in physiological buffer and in the gas phase. High-mass calibration in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has remained a problem due to the lack of suitable standards. Large proteins can hardly be freed of their substructural microheterogeneity by classical purification procedures so that their use as calibrants is limited. A small adduct-forming protein of validated quality is a valuable alternative for that purpose.Methodology/Principal Findings
Three major PHP clusters of ∼113, 209 and >600 kDa were observed in gel filtration analysis. Re-chromatography of the monomer peak showed the same cluster distribution. The tendency to associate was detected also in MALDI-TOF MS measuring regular adducts up to 200 kDa.Conclusions/Significance
PHP forms multimers consisting of up to more than 35 protein molecules. In MALDI-TOF MS it generates adduct ions every 16 kDa. The protein can be produced with high quality so that its use as calibration compound for high mass ranges above 100 kDa, where standards are difficult to obtain, is feasible. 相似文献13.
Background
Podocyte injury and subsequent excretion in urine play a crucial role in the pathogenesis and progression of diabetic nephropathy (DN). Quantification of messenger RNA (mRNA) expression in urinary sediment by real-time PCR is emerging as a noninvasive method of screening DN-associated biomarkers. We hypothesized that the urinary mRNA profile of podocyte-associated molecules may provide important clinical insight into the different stages of diabetic nephropathy.Methods
DN patients (N = 51) and healthy controls (N = 13) were enrolled in this study. DN patients were divided into a normoalbuminuria group (UAE<30 mg/g, n = 17), a microalbuminuria group (UAE 30∼300 mg/g, n = 15), and a macroalbuminuria group (UAE>300 mg/g, n = 19), according to their urinary albumin excretion (UAE). Relative mRNA abundance of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were quantified, and correlations between target mRNAs and clinical parameters were examined.Results
The urinary mRNA levels of all genes studied were significantly higher in the DN group compared with controls (p<0.05), and mRNA levels increased with DN progression. Urinary mRNA levels of all target genes positively correlated with both UAE and BUN. The expression of podocalyxin, CD2-AP, α-actin4, and podocin mRNA correlated with serum creatinine (r = 0.457, p = 0.001; r = 0.329, p = 0.01; r = 0.286, p = 0.021; r = 0.357, p = 0.006, respectively). Furthermore, podocalyxin mRNA was found to negatively correlate with eGFR (r = −0.349, p = 0.01).Conclusion
The urinary mRNA profiles of synaptopodin, podocalyxin, CD2-AP, α-actin4, and podocin were found to increase with the progression of DN, which suggested that quantification of podocyte-associated molecules will be useful biomarkers of DN. 相似文献14.
Eun Young Lee Sang Soo Kim Ji-Sung Lee In Joo Kim Sang Heon Song Seung-Kuy Cha Kyu-Sang Park Jeong Suk Kang Choon Hee Chung 《PloS one》2014,9(8)
Objective
Although α-klotho is known as an anti-aging, antioxidant, and cardio-renal protective protein, the clinical implications of soluble α-klotho levels in patients with diabetes have not been evaluated. Therefore, this study evaluated whether plasma and urinary α-klotho levels are associated with albuminuria in kidney disease in diabetes.Research Design and Methods
A total of 147 patients with type 2 diabetes and 25 healthy control subjects were enrolled. The plasma and urine concentrations of α-klotho were analyzed by enzyme-linked immunosorbent assay.Results
Plasma α-klotho (572.4 pg/mL [95% CI, 541.9–604.6 pg/mL] vs. 476.9 pg/mL [95% CI, 416.9–545.5 pg/mL]) and urinary α-klotho levels (59.8 pg/mg creatinine [95% CI, 43.6–82.0 pg/mg creatinine] vs. 21.0 pg/mg creatinine [95% CI, 9.7–45.6 pg/mg creatinine]) were significantly higher in diabetic patients than non-diabetic controls. Among diabetic patients, plasma α-klotho concentration was inversely associated with albuminuria stages (normoalbuminuria, 612.6 pg/mL [95% CI, 568.9–659.6 pg/mL], microalbuminuria, 551.8 pg/mL [95% CI, 500.5–608.3 pg/mL], and macroalbuminuria, 505.7 pg/mL [95% CI, 439.7–581.7 pg/mL] (p for trend = 0.0081), while urinary α-klotho levels were remained constantly high with increasing urinary albumin excretion.Conclusions
Soluble α-klotho levels in plasma and urine may be novel and useful early markers of diabetic renal injury. 相似文献15.
Yamauchi Y Izumi Y Kawamura M Nakatsuka S Yashiro H Tsukada N Inoue M Asakura K Nomori H 《PloS one》2011,6(11):e27086
Objective
To evaluate the safety and efficacy of cryoablation for metastatic lung tumors from colorectal cancer.Methods
The procedures were performed on 24 patients (36–82 years of age, with a median age of 62; 17 male patients, 7 female patients) for 55 metastatic tumors in the lung, during 30 sessions. The procedural safety, local progression free interval, and overall survival were assessed by follow-up computed tomographic scanning performed every 3–4 months.Results
The major complications were pneumothorax, 19 sessions (63%), pleural effusion, 21 sessions (70%), transient and self-limiting hemoptysis, 13 sessions (43%) and tract seeding, 1 session (3%). The 1- and 3-year local progression free intervals were 90.8% and 59%, respectively. The 3-years local progression free intervals of tumors ≤15 mm in diameter was 79.8% and that of tumors >15 mm was 28.6% (p = 0.001; log-rank test). The 1- and 3-year overall survival rates were 91% and 59.6%, respectively.Conclusion
The results indicated that percutaneous cryoablation is a feasible treatment option. The local progression free interval was satisfactory at least for tumors that were ≤15 mm in diameter. 相似文献16.
Buurman BM Hoogerduijn JG de Haan RJ Abu-Hanna A Lagaay AM Verhaar HJ Schuurmans MJ Levi M de Rooij SE 《PloS one》2011,6(11):e26951
Background
To study the prevalence of eighteen geriatric conditions in older patients at admission, their reporting rate in discharge summaries and the impact of these conditions on mortality and functional decline one year after admission.Method
A prospective multicenter cohort study conducted between 2006 and 2008 in two tertiary university teaching hospitals and one regional teaching hospital in the Netherlands. Patients of 65 years and older, acutely admitted and hospitalized for at least 48 hours, were invited to participate. Eighteen geriatric conditions were assessed at hospital admission, and outcomes (mortality, functional decline) were assessed one year after admission.Results
639 patients were included, with a mean age of 78 years. IADL impairment (83%), polypharmacy (61%), mobility difficulty (59%), high levels of primary caregiver burden (53%), and malnutrition (52%) were most prevalent. Except for polypharmacy and cognitive impairment, the reporting rate of the geriatric conditions in discharge summaries was less than 50%. One year after admission, 35% had died and 33% suffered from functional decline. A high Charlson comorbidity index score, presence of malnutrition, high fall risk, presence of delirium and premorbid IADL impairment were associated with mortality and overall poor outcome (mortality or functional decline). Obesity lowered the risk for mortality.Conclusion
Geriatric conditions were highly prevalent and associated with poor health outcomes after admission. Early recognition of these conditions in acutely hospitalized older patients and improving the handover to the general practitioner could lead to better health outcomes and reduce the burden of hospital admission for older patients. 相似文献17.
Sanne R. Martens-de Kemp Simone U. Dalm Fiona M. J. Wijnolts Arjen Brink Richard J. Honeywell Godefridus J. Peters Boudewijn J. M. Braakhuis Ruud H. Brakenhoff 《PloS one》2013,8(4)
Purpose
The combination of systemic cisplatin with local and regional radiotherapy as primary treatment of head and neck squamous cell carcinoma (HNSCC) leads to cure in approximately half of the patients. The addition of cisplatin has significant effects on outcome, but despite extensive research the mechanism underlying cisplatin response is still not well understood.Methods
We examined 19 HNSCC cell lines with variable cisplatin sensitivity. We determined the TP53 mutational status of each cell line and investigated the expression levels of 11 potentially relevant genes by quantitative real-time PCR. In addition, we measured cisplatin accumulation and retention, as well as the level of platinum-DNA adducts.Results
We found that the IC50 value was significantly correlated with the platinum-DNA adduct levels that accumulated during four hours of cisplatin incubation (p = 0.002). We could not find a significant correlation between cisplatin sensitivity and any of the other parameters tested, including the expression levels of established cisplatin influx and efflux transporters. Furthermore, adduct accumulation did not correlate with mRNA expression of the investigated influx pumps (CTR1 and OCT3) nor with that of the examined DNA repair genes (ATR, ATM, BRCA1, BRCA2 and ERCC1).Conclusion
Our findings suggest that the cisplatin-DNA adduct level is the most important determinant of cisplatin sensitivity in HNSCC cells. Imaging with radio-labeled cisplatin might have major associations with outcome. 相似文献18.
Background
Proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing.Principal Findings
In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%). Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis) of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates.Conclusions
These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form suitable for proteomic analysis. 相似文献19.
de Torres JP Casanova C Pinto-Plata V Varo N Restituto P Cordoba-Lanus E Baz-Dávila R Aguirre-Jaime A Celli BR 《PloS one》2011,6(1):e16021
Rationale
Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).Hypothesis
There are differences in serum biomarker levels between women and men with COPD.Objective
Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.Methods
We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD.Results
The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes.Conclusions
In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings. 相似文献20.
C��cile Tol��dano Murielle Gain Adrien Kettaneh Bruno Baudin Catherine Johanet Patrick Ch��rin S��bastien Rivi��re Jean Cabane Kiet Phong Tiev 《Arthritis research & therapy》2012,14(3):R152