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151.
Kiritsi D He Y Pasmooij AM Onder M Happle R Jonkman MF Bruckner-Tuderman L Has C 《The Journal of clinical investigation》2012,122(5):1742-1746
Spontaneous gene repair, also called revertant mosaicism, has been documented in several genetic disorders involving organs that undergo self-regeneration, including the skin. Genetic reversion may occur through different mechanisms, and in a single individual, the mutation can be repaired in various ways. Here we describe a disseminated pattern of revertant mosaicism observed in 6 patients with Kindler syndrome (KS), a genodermatosis caused by loss of kindlin-1 (encoded by FERMT1) and clinically characterized by patchy skin pigmentation and atrophy. All patients presented duplication mutations (c.456dupA and c.676dupC) in FERMT1, and slipped mispairing in direct nucleotide repeats was identified as the reversion mechanism in all investigated revertant skin spots. The sequence around the mutations demonstrated high propensity to mutations, favoring both microinsertions and microdeletions. Additionally, in some revertant patches, mitotic recombination generated areas with homozygous normal keratinocytes. Restoration of kindlin-1 expression led to clinically and structurally normal skin. Since loss of kindlin-1 severely impairs keratinocyte proliferation, we predict that revertant cells have a selective advantage that allows their clonal expansion and, consequently, the improvement of the skin condition. 相似文献
152.
Mitsani D Nguyen MH Shields RK Toyoda Y Kwak EJ Silveira FP Pilewski JM Crespo MM Bermudez C Bhama JK Clancy CJ 《Antimicrobial agents and chemotherapy》2012,56(5):2371-2377
Voriconazole prophylaxis is common following lung transplantation, but the value of therapeutic drug monitoring is unknown. A prospective, observational study of lung transplant recipients (n = 93) receiving voriconazole prophylaxis was performed. Serum voriconazole troughs (n = 331) were measured by high-pressure liquid chromatography. The median initial and subsequent troughs were 1.91 and 1.46 μg/ml, respectively. The age of the patient directly correlated with initial troughs (P = 0.005). Patients that were ≥ 60 years old and cystic fibrosis patients were significantly more likely to have higher and lower initial troughs, respectively. In 95% (88/93) of patients, ≥ 2 troughs were measured. In 28% (25/88) and 32% (28/88) of these patients, all troughs were ≤ 1.5 μg/ml or >1.5 μg/ml, respectively. Ten percent (10/93) and 27% (25/93) of the patients developed invasive fungal infection (tracheobronchitis) and fungal colonization, respectively. The median troughs at the times of positive and negative fungal cultures were 0.92 and 1.72 μg/ml (P = 0.07). Invasive fungal infections or colonization were more likely with troughs of ≤ 1.5 μg/ml (P = 0.01) and among patients with no trough of >1.5 μg/ml (P = 0.007). Other cutoff troughs correlated less strongly with microbiologic outcomes. Troughs correlated directly with aspartate transferase levels (P = 0.003), but not with other liver enzymes. Voriconazole was discontinued due to suspected toxicity in 27% (25/93) of the patients. The troughs did not differ at the times of suspected drug-induced hepatotoxicity, central nervous system (CNS) toxicity, or nausea/vomiting and in the absence of toxicity. Voriconazole prophylaxis was most effective at troughs of >1.5 μg/ml. A cutoff for toxicity was not identified, but troughs of >4 μg/ml were rare. The data support a target range of >1.5 to 4 μg/ml. 相似文献
153.
154.
Dimopoulou I Nikitas N Orfanos SE Theodorakopoulou M Vassiliadi D Ilias I Ikonomidis I Boutati E Maratou E Tsangaris I Karkouli G Tsafou E Diamantakis A Kopterides P Maniatis N Kotanidou A Armaganidis A Ungerstedt U 《Shock (Augusta, Ga.)》2011,35(4):343-348
Microdialysis (MD) provides the opportunity to monitor tissue metabolic changes. This study aimed to describe the kinetics of MD-derived metabolites during the course of critical sepsis, to assess whether these metabolites are useful in grading sepsis severity, and to investigate their prognostic use. To this end, 54 mechanically ventilated septic patients were prospectively studied, out of which 39 had shock. Upon sepsis onset, an MD catheter was inserted into the subcutaneous adipose tissue of the upper thigh. Dialysate samples were analyzed for glucose, pyruvate, lactate, and glycerol. Sampling was performed six times per day for a maximum of 6 days. The daily mean values of MD measurements were calculated for each patient. Arterial blood was analyzed for glucose, lactate, and glycerol concomitantly with dialysate sampling. Blood glucose and tissue glucose levels along with lactate levels were high during the entire study period. Tissue pyruvate and glycerol were also raised, whereas the lactate-pyruvate ratio was preserved. At study entry, patients with septic shock had higher tissue lactate (3.3 vs. 1.9 mmol/L, P = 0.01) and glycerol (340 vs. 169 μmol/L, P = 0.04) levels compared with those without shock. Nonsurvivors had higher tissue lactate (P = 0.008), glycerol (P = 0.004), and pyruvate (P = 0.002) levels than survivors during the whole observation period. Logistic regression analysis showed that age (odds ratio [OR], 1.075; 95% confidence interval [CI], 1.004-1.150; P = 0.03), Sequential Organ Failure Assessment score on day 1 (OR, 1.550; 95% CI, 1.043-2.312; P = 0.03), and tissue glycerol on day 1 (OR, 1.007; 95% CI, 1.001-1.012; P = 0.01) predicted mortality independently. In conclusion, critical sepsis is characterized by high tissue lactate and pyruvate levels and a preserved lactate-pyruvate ratio, suggesting a nonischemic mechanism for raised blood lactate levels. Septic shock is associated with higher tissue lactate and glycerol levels compared with sepsis without shock. Elevated tissue lactate, pyruvate, and glycerol levels are related to poor clinical outcome, with the latter constituting an independent predictor. 相似文献
155.
Kastritis E Kyrtsonis MC Hatjiharissi E Symeonidis A Michalis E Repoussis P Tsatalas K Michael M Sioni A Kartasis Z Stefanoudaki E Voulgarelis M Delimpasi S Gavriatopoulou M Koulieris E Gika D Vervesou E Konstantopoulos K Kokkini G Zomas A Roussou P Anagnostopoulos N Economopoulos T Terpos E Zervas K Dimopoulos MA 《American journal of hematology》2011,86(6):479-483
The treatment of Waldenström's macroglobulinemia (WM) has changed over the last decades, mainly because of the introduction of nucleoside analogues and of rituximab while novel agents such as bortezomib have been recently introduced. We performed an analysis to investigate whether the outcome of patients with WM has improved over the last years, compared to that of patients who started treatment before new drugs became widely available, especially as part of the frontline treatment. We analyzed 345 symptomatic patients with WM: 130 who initiated treatment before and 215 who started treatment after January 1, 2000. Patients who started treatment in the latter group were older and had more often elevated beta2‐microglobulin but the other characteristics were similar between the two groups. Most patients who started treatment before January 1, 2000 were treated upfront with alkylating agent‐based regimens and most patients who started treatment after January 1, 2000 received rituximab‐based regimens as initial treatment. Objective response (63 and 59%, respectively) and median overall survival, OS, (106.5 months for Group A and is estimated at 94 months for Group B, P = 0.327) were similar. There was also no difference regarding OS or cause specific survival (CSS) in each risk group according to IPSSWM. Our observation may be explained by the indolent course of WM in several patients and by the lack of profound cytoreduction in patients with high‐risk disease. Possible differences in the 15‐ or 20‐year survival rate between the two groups may be detected with further follow‐up of these patients. Am. J. Hematol. 2011. © 2011 Wiley‐Liss, Inc. 相似文献
156.
Dimitra Vernardou 《Materials》2021,14(15)
The goal of the battery research community is to reach sustainable batteries with high performance, meaning energy and power densities close to the theoretical limits, excellent stability, high safety, and scalability to enable the large-scale production of batteries at a competitive cost. In that perspective, chemical vapour deposition processes, which can operate safely under high-volume conditions at relatively low cost, should allow aqueous batteries to become leading candidates for energy storage applications. Research interest and developments in aqueous battery technologies have significantly increased the last five years, including monovalent (Li+, Na+, K+) and multivalent systems (Mg2+, Zn2+, Al3+). However, their large-scale production is still somewhat inhibited, since it is not possible to get electrodes with robust properties that yield optimum performance of the electrodes per surface area. In this review paper, we present the progress and challenges in the growth of electrodes through chemical vapour deposition at atmospheric pressure, which is one procedure that is proven to be industrially competitive. As battery systems attract the attention of many researchers, this review article might help those who work on large-scale electrical energy storage. 相似文献
157.
Panagiotis Mallis Dimitra Boulari Panagiota Chachlaki Catherine Stavropoulos Giokas Efstathios Michalopoulos 《Gynecological endocrinology》2020,36(2):139-142
AbstractWharton’s Jelly (WJ) tissue is a promising biomaterial, for tissue engineering applications. However, its preservation over a long period in order to be readily available needs further optimization. A possible solution could be the vitrification and storage of WJ tissue at low temperatures. The aim of this study is to evaluate the effect of low temperature in the WJ tissue, which was stored at ?196?°C, either with the vitrification or conventional cryopreservation methods. WJ tissues were isolated from human umbilical cords, cryopreserved with the above methods and remained for 1?year at ?196?°C. Histological analysis of tissue’s extracellular matrix (ECM), isolation, and characterization of mesenchymal stromal cells (MSCs) were performed. Histological analysis revealed the presence of ECM components such as collagen, sulfated glycosaminoglycans (sGAGs), and the presence of cell nuclei only in vitrified samples. Furthermore, MSCs were isolated and expanded successfully from vitrified WJ tissues, whereas a few viable cells were obtained from conventionally cryopreserved tissues that were not further expanded. In conclusion, this study indicated the proper preservation of vitrified WJ tissues after 1?year of storage, which eventually could be used in tissue engineering and regenerative medicine approaches. 相似文献
158.
Sabine Fuchs Britta Olberg Matthias Perleth Reinhard Busse Dimitra Panteli 《Health policy (Amsterdam, Netherlands)》2019,123(2):173-181
Objective
Medical devices (MDs) encompass a broad and heterogeneous range of technologies. While practices vary considerably across countries, MDs often find application in patient care with little or no evaluation of their effectiveness and safety following market approval. A recently proposed taxonomy of MDs considered devices from the viewpoint of Health Technology Assessment (HTA). The aim of the work presented here was to test its plausibility and applicability by considering real-world HTA practices.Methods
HTA reports on MDs from European institutions were collected in a systematic manner and the evaluated devices and/or related procedures were matched to a position on the taxonomy. Following this, representatives from 16 European HTA institutions were asked about the usefulness of the taxonomy in semi-structured interviews.Results
1237 HTA reports (2004–2015) from 33 European institutions were included in the sample. The majority of reports was on technologies from the taxonomic positions initially estimated as having high relevance. Most of the experts interviewed stated that they found the taxonomy useful, particularly regarding its potential to aid in selecting technologies for assessment and to highlight potential methodological particularities per taxonomic position.Conclusions
Overall, the distribution of identified reports on the matrix confirmed that the initial estimation of the relevance and necessity of HTA provided in the taxonomic model is plausible. In addition, interviews with representatives of European HTA institutions showed that the taxonomy could be useful. 相似文献159.
Background and aims
There is little guidance regarding the evaluation and management of patients with Staphylococcus aureus bacteriuria (SABU). Here, we aimed to provide an up-to-date review of the literature.Methods
We searched PubMed, Scopus, and clinical trial registries for articles evaluating the epidemiology of SABU, risk factors of SABU, the association of SABU with urinary tract infection, bacteremia and invasive S. aureus infections, and the management of patients with SABU.Results
S. aureus is an uncommon isolate in urine cultures. It is more common among certain patients, e.g., patients with indwelling urinary tract devices or prior urinary tract instrumentation. SABU may represent asymptomatic bacteriuria, primary urinary tract infection, or hematogenous seeding of the urinary tract associated with other foci of infection. SABU may also serve as the focus for subsequent bacteremia and invasive infections. We did not find any clinical trials regarding the management of patients with SABU.Conclusions
Based on our review, we suggest an algorithmic approach for the evaluation and management of patients with SABU. However, evidence from clinical trials is lacking and there are severalgaps in the current literature. These are discussed in this review.160.
Iosif Strouthos Nikolaos Tselis Georgios Chatzikonstantinou Saeed Butt Dimos Baltas Dimitra Bon Natasa Milickovic Nikolaos Zamboglou 《Radiotherapy and oncology》2018,126(2):270-277