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11.
《JACC: Cardiovascular Imaging》2014,7(10):1001-1010
ObjectivesThe purpose of this study was to evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk.BackgroundDespite the close association of diabetes and CAD, general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking.MethodsProspective multicenter outcome study—with a pilot randomized treatment substudy. The study comprised 400 asymptomatic patients with DM (type 2) without history or symptoms of CAD at high CAD risk. They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography (MPS) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management.ResultsAn abnormal MPS was found in 87 of 400 patients (22%). In patients with normal MPS, MACE occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio: 3.44; 95% confidence interval [CI]: 1.32 to 8.95; p = 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in “overt or silent CAD progression” of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates (p = 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001).ConclusionsHigh-risk asymptomatic patients with DM and normal MPS (78%) have a low rate of first manifestations of CAD. Patients with abnormal MPS at baseline (22%) have a 7-fold higher rate of progression to “overt or silent CAD,” despite therapy. Randomized patients’ outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone. (Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632). 相似文献
12.
《JACC: Cardiovascular Imaging》2014,7(11):1130-1148
Bioresorbable vascular scaffolds (BRS) represent a novel approach to provide transient vessel support to drug-delivery capability without the long-term limitations of metallic drug-eluting stents (DES). The technology has the potential to overcome many of the safety concerns associated with metallic DES and possibly even convey further clinical benefit. In particular, the BRS are designed to provide short-term lumen support, and after being completely bioresorbed, eliminate the permanent caging typical of metallic DES. However, this technology has required new imaging modalities and methodologies for its assessment because the design, degradation rate, loss of mechanical property, and drug deliverability may affect its safety and efficacy. We provide an overview of all existing methods for assessing bioresorbable devices, from noninvasive to invasive, from light to sound based, and from morphological to functional parameters. 相似文献
13.
MicroRNA (miRNA) expression profiling is gaining interest in the forensic community because the intrinsically short fragment and tissue-specific expression pattern enable miRNAs as a useful biomarker for body fluid identification. Measuring the quantity of miRNAs in forensically relevant body fluids is an important step to screen specific miRNAs for body fluid identification. The recent introduction of massively parallel sequencing (MPS) has the potential for screening miRNA biomarkers at the genome-wide level, which allows both the detection of expression pattern and miRNA sequences. In this study, we employed the Ion Personal Genome Machine® System (Ion PGM™ System, Thermo Fisher) to characterize the distribution and expression of 2588 human mature miRNAs (miRBase v21) in 5 blood samples and 5 saliva samples. An average of 1,885,000 and 1,356,000 sequence reads were generated in blood and saliva respectively. Based on miRDong, a Perl-based tool developed for semi-automated miRNA distribution designations, and manually ascertained, 6 and 19 miRNAs were identified respectively as potentially blood and saliva-specific biomarkers. Herein, this study describes a complete and reliable miRNA workflow solution based on Ion PGM™ System, starting from efficient RNA extraction, followed by small RNA library construction and sequencing. With this workflow solution and miRDong analysis it will be possible to measure miRNA expression pattern at the genome-wide level in other forensically relevant body fluids. 相似文献
14.
Dinesh K. Mishra Ruchita Shandilya Pradyumna K. Mishra 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(7):2023-2050
Over the recent couple of decades, pharmaceutical field has embarked most phenomenal noteworthy achievements in the field of medications as well as drug delivery. The rise of Nanotechnology in this field has reformed the existing drug delivery for targeting, diagnostic, remedial applications and patient monitoring. The convincing usage of nanotechnology in the conveyance of medications that prompts an extension of novel lipid-based nanocarriers and non-liposomal systems has been discussed. Present review deals with the late advances and updates in lipidic nanocarriers, their formulation strategies, challenging aspects, stability profile, clinical applications alongside commercially available products and products under clinical trials. This exploration may give a complete idea viewing the lipid based nanocarriers as a promising choice for the formulation of pharmaceutical products, the challenges looked by the translational process of lipid-based nanocarriers and the combating methodologies to guarantee the headway of these nanocarriers from bench to bedside. 相似文献
15.
Fengling Wang Xi Ye Yifan Wu Huihui Wang Chengming Sheng Daiyin Peng Weidong Chen 《Journal of pharmaceutical sciences》2019,108(1):641-651
Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon. 相似文献
16.
Klane K. White Andrea Jester C. Edward Bache Paul R. Harmatz Renée Shediac Mihir M. Thacker William G. Mackenzie 《Journal of children's orthopaedics》2014,8(4):295-304
Background
Musculoskeletal involvement in Morquio A syndrome (mucopolysaccharidosis IVA; MPS IVA) contributes significantly to morbidity and mortality. While the spinal manifestations of the disorder have received considerable attention in the literature, there have been few reported studies to date to guide the management of the orthopedic problems associated with the lower and upper extremities.Purpose
The objective was to develop recommendations for the management of the extremities in patients with Morquio A syndrome.Methods
A group of specialists in orthopedics, pediatrics and genetics with experience in the management of Morquio A patients convened to review and discuss current clinical practices and to develop preliminary recommendations. Evidence from the literature was retrieved. Recommendations were further refined until consensus was reached.Results and conclusions
This present article provides a detailed review and discussion of the lower and upper extremity deformities in Morquio A syndrome and presents recommendations for the assessment and treatment of these complications. Key issues, including the importance of early diagnosis and the implications of medical therapy, are also addressed. The recommendations herein represent an attempt to develop a uniform and practical approach to managing patients with Morquio A syndrome and improving their outcomes. 相似文献17.
Mohanram Narayanan Oleh Pankewycz Fuad Shihab Anne Wiland Kevin McCague Laurence Chan 《Clinical transplantation》2014,28(2):184-191
Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four‐yr data on 904 patients receiving tacrolimus and enteric‐coated mycophenolate sodium (EC‐MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non‐AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non‐AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC‐MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non‐AA patients. Biopsy‐proven acute rejection was higher in AA vs. non‐AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non‐AA patients. Kidney allograft survival remains lower for AA vs. non‐AA recipients even under the current standard of care. 相似文献
18.
19.
Kyoko Nagao Thierry Morlet Elizabeth Haley Jennifer Padilla Julianne Nemith Robert W. Mason Shunji Tomatsu 《Molecular genetics and metabolism》2018,123(4):472-478
Background
Hearing impairment is a common problem in patients with mucopolysaccharidosis IV (MPS IV) throughout their life. Many of the adult patients with MPS IV exhibit permanent or severe hearing loss. However, there has been no systematic review of detailed audiological test results in MPS IV.Materials and methods
Fourteen individuals with MPS IV (13 MPS IVA and 1 MPS IVB; aged between 12 and 38?years old) participated in the current study. We obtained auditory neurophysiological responses (auditory brainstem responses and otoacoustic emissions test) in addition to pure-tone audiometry and middle ear function tests (tympanometry and acoustic reflexes).Results
The results indicated various levels and types of hearing loss with abnormal neurophysiological responses even in those patients with MPS IVA with normal pure tone thresholds. We also found a strong relationship between height (short stature is an indicator of skeletal severity) and hearing sensitivity as well as a strong relationship between height and outer hair cell function in the inner ear (measured by otoacoustic emissions) among MPS IVA patients.Conclusion
The strong correlation between reduced height and hearing loss indicates that patients with severe skeletal dysplasia may be at higher risk of developing more severe hearing loss. More importantly, the spectrum of hearing disorders indicates that MPS IV patients should have annual neurophysiological hearing tests in addition to audiometric testing from an early age regardless of their skeletal severity to more carefully monitor disease progression. 相似文献20.
Clare E. Beesley Elisabeth P. Young Niamh Finnegan Marie Jackson Kevin Mills Ashok Vellodi Maureen Cleary Bryan G. Winchester 《Molecular genetics and metabolism》2009,96(4):218-224
Surface enhanced laser desorption/ionisation time of flight (SELDI-TOF) mass spectrometry has been used to search for new protein biomarkers in the plasma of patients with mucopolysacharidoses (MPS). Differences in the levels of some plasma proteins, particularly the apolipoprotein ApoCI, were observed between MPS patients and normal controls, using the different chromatographic surfaces (ProteinChips®). ApoCI was identified by both its mass and by immunological techniques. In plasma, it exists in two forms, ApoCI and a truncated form which lacks two N-terminal amino acids, ApoCI′. In controls, the ratio of ApoCI′:ApoCI observed using the cation-exchange surface (CM10) was approximately 1:2 whereas in most MPS patients it varied from 1:1 to 1:0.8. The ratio of ApoCI′:ApoCI in plasma is determined by the activity of dipeptidyl peptidase IV, DPP-IV (also known as the leucocyte antigen CD26), which was found to be elevated up to 3-fold in MPS patients. The DPP-IV activity decreased in MPS I patients undergoing enzyme replacement therapy, indicating that it could be a useful biomarker for monitoring the efficacy of treatment in MPS disease. As DPP-IV has an important regulatory role in metabolism, it is possible that its elevation could cause some of the secondary pathology in MPS, and inhibition of DPP-IV might have a role in MPS therapy. 相似文献