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41.
Hermine A van Duyvenvoorde Julian C Lui Sarina G Kant Wilma Oostdijk Antoinet CJ Gijsbers Mari?tte JV Hoffer Marcel Karperien Marie JE Walenkamp Cees Noordam Paul G Voorhoeve Verónica Mericq Alberto M Pereira Hedi L Claahsen-van de Grinten Sandy A van Gool Martijn H Breuning Monique Losekoot Jeffrey Baron Claudia AL Ruivenkamp Jan M Wit 《European journal of human genetics : EJHG》2014,22(5):602-609
Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes. 相似文献
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Maria das Gra?as WS Coriolano Luciana R Belo Danielle Carneiro Amdore G Asano Paulo José AL Oliveira Douglas Monteiro da Silva Otávio G Lins 《Dysphagia》2012,27(4):550-555
Our goal was to study deglutition of Parkinson??s disease (PD) patients and normal controls (NC) using surface electromyography (sEMG). The study included 15 patients with idiopathic PD and 15 age-matched normal controls. Surface electromyography was collected over the suprahyoid muscle group. Conditions were the following: swallow at once 10 and 20?ml of water and 5 and 10?ml of yogurt of firm consistency, and freely drink 100?ml of water. During swallowing, durations of sEMG were significantly longer in PD patients than in normal controls but no significant differences of amplitudes were found. Eighty percent of the PD patients and 20?% of the NC needed more than one swallow to consume 20?ml of water, while 70?% of the PD patients and none of the NC needed more than one swallow to consume 5?ml of yogurt. PD patients took significantly more time and needed significantly more swallows to drink 100?ml of water than normal controls. We conclude that sEMG might be a simple and useful tool to study and monitor deglutition in PD patients. 相似文献
44.
GEMMA PELARGONIO MARIA L. NARDUCCI ELEONORA RUSSO MICHELA CASELLA PASQUALE SANTANGELI ROBERT CANBY AMIN AL‐AHMAD LARRY D. PRICE LUIGI DI BIASE CANDICE J. KWARK MARK HARWOOD FRANCESCO PERNA GIANLUIGI BENCARDINO CAROLINA IERARDI ENRICO M. TRECARICHI ENRICA SANTELLI MARIO TUMBARELLO PRASANT MOHANTY SHANE BAILEY JOHN DAVID BURKHARDT FULVIO BELLOCCI ANDREA NATALE ANTONIO DELLO RUSSO 《Journal of cardiovascular electrophysiology》2012,23(10):1103-1108
Transvenous Lead Extraction . Introduction: As the population ages, the number of elderly patients with implantable cardiac devices referred for transvenous lead extraction will dramatically increase in Western countries. The safety and effectiveness of lead extraction in elderly patients has not been well evaluated. We report the safety and effectiveness of transvenous lead extraction in octogenarians. Methods and Results: From January 2005 to January 2011, we reviewed data from consecutive patients ≥ 80 years referred to our institutions for transvenous lead extraction because of cardiac device infection or lead malfunction. Clinical characteristics, procedural features, and periprocedural major and minor complications were compared between octogenarians and younger patients. Out of 849 patients undergoing lead extraction in the participating institutions during the study period, 150 (18%) patients were octogenarians (mean age 84 years; range 80–96; 64% males). A significantly higher percentage of octogenarians presented with chronic renal failure (55% vs 26%; P < 0.001), history of malignancy (22% vs 6%; P < 0.001), and chronic obstructive pulmonary disease (46% vs 19%; P < 0.001). Complete lead extraction rates were similar in the 2 age groups (97% in octogenarians vs 96% in patients <80 years; P = 0.39). Periprocedural death occurred in 2 (1.3%) patients ≥80 years and in 5 (0.72%) patients <80 years (P = 0.45 for comparison). No differences in terms of other periprocedural major and minor complications were found between the 2 age groups. Conclusion: Despite presenting with a significantly higher rate of comorbidities, transvenous lead extraction can be performed safely and successfully in octogenarians. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1103‐1108, October 2012) 相似文献
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46.
Nicolau DP Sutherland C Winget D Baughman RP 《Pulmonary pharmacology & therapeutics》2012,25(1):94-98
While previous reports have described the bronchopulmonary profile of the fluoroquinolones in healthy volunteers, limited data are available in infected patients. The purpose of this study was to determine the intrapulmonary profile of high-dose (750 mg) levofloxacin in patients during an acute exacerbation of chronic bronchitis (AECB). Twenty-four patients experiencing clinical signs and symptoms of AECB were enrolled. Once enrolled, patients received levofloxacin 750 mg once daily × 5 days. Bronchoalveolar lavage aspirates and simultaneous plasma samples were obtained at 4 h, 12 h or 24 h after the third dose. Concentrations in biologic matrixes were determined with a validated HPLC method. Epithelial lining fluid (ELF) concentrations were calculated using the urea dilution method. Five patients did not complete the trial, 19 patients underwent bronchoscopy, 18 (52 ± 13 yrs) had sufficient samples for analysis and confirmed medication compliance. Mean plasma concentrations at 4, 12, and 24 h were 8.0 ± 2.5, 5.8 ± 1.2, and 2.2 ± 1.2 μg/mL. Mean ELF values at 4, 12, and 24 h were 7.5 ± 3.0, 8.3 ± 6.0, and 1.2 ± 0.9 μg/mL. Mean alveolar macrophage (AM) concentrations at 4, 12, and 24 h were 38.5 ± 43.7, 13.4 ± 14.4, and 9.0 ± 7.5 μg/mL. The penetration (ELF/plasma ratio) into the infection site was 113%. In these subjects with AECB, levofloxacin 750 mg once daily reached adequate exposures in the plasma, ELF, and AMs for the most commonly associated pathogens. 相似文献
47.
Percutaneous balloon aortic valvotomy was attempted in six consecutiveadolescents and young adults, (meanage 18 ± 5 years),with severe congenital aortic valvular stenosis. Peak systolicaortic valve gradient measurement and aortography was performedbefore and immediately after valvotomy, and a 16 monthsfollow-up. The single-balloon technique was used in two patientsand the double-balloon technique in four patients. After balloonvalvotomy the mean peak systolic aortic valve gradient (PSG)decreased from 122 ± 53 to 43 ± 20 mmHg (P >001). The haemodynamic improvement persisted at follow-up (PSG= 47 ±31 mmHg), except in one patient who had previouslyundergone aortic surgical valvotomy. One balloon valvotomy wasunsuccessful, presumably because of the selection of an inappropriatelysmall balloon. Two patients with critical aortic stenosis (PSG>165mmHg), who exhibited a thick aortic valve on echocardiographywith a relatively small aortic root and annulus, had a dramaticreduction in PSG. However, the degree of aortic regurgitationincreased significantly in both cases. The theoretical haemodynamicadvantage of the double versus the single balloon techniqueswas confirmed in one patient. We have demonstrated that percutaneousballoon aortic valvotomy using either the single- or double-balloontechnique is feasible in young adults with severe congenitalaortic stenosis. Further studies are required both to defineappropriate patients and the selection of balloon diameter andlength. 相似文献
48.
Translational regulation of the L11 ribosomal protein operon of Escherichia coli: analysis of the mRNA target site using oligonucleotide-directed mutagenesis. 总被引:8,自引:1,他引:8 下载免费PDF全文
G Baughman M Nomura 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(17):5389-5393
The L11 ribosomal protein operon in Escherichia coli consists of the genes for proteins L11 and L1 and is feedback regulated by the translational repressor L1. The mRNA target site for this repression is located close to the translation initiation site of the first L11 cistron. Several mutant plasmid molecules carrying altered nucleotide sequences in the L1 target site were constructed by site-directed in vitro mutagenesis using synthetic oligodeoxyribonucleotides. Specifically, we examined the importance of a presumptive double-stranded stem structure that is common among L1 binding sites on rRNA from a variety of organisms and in L11 mRNA. Mutational alterations that disrupt the stem structure were found to abolish translational regulation as analyzed both in vitro and in vivo. Two of the mutations were combined so that the stem structure was restored but with a different primary nucleotide sequence. This double mutant was shown to restore the original phenotype, the ability to be translationally regulated by L1. These experiments show the importance of the stem structure, but not its primary sequence, for the interaction of L1 with the mRNA and support the concept that mRNA target sites share some structural features with the corresponding ribosomal protein binding sites of rRNA. 相似文献
49.
Hutchins SS Baughman AL Orr M Haley C Hadler S 《The Journal of infectious diseases》2004,189(Z1):S108-S115
Knowledge of the minimum level of vaccination capable of preventing measles transmission in an age group is helpful for establishing program targets for measles elimination. In 1990, during the measles resurgence in the United States, one-half of cases occurred in children aged <5 years. Although estimated population immunity among persons >or=6 years of age was 93%, immunity was lower and varied widely among preschool-aged children. To examine the association of vaccine coverage at 2 years of age and measles incidence among preschool-aged children, we analyzed ecological studies of measles incidence in Milwaukee (Wisconsin) census tracts, Dallas (Texas) ZIP code areas, and selected cities during the 1989-1991 measles resurgence. In each study area, measles incidence decreased rapidly with increasing measles vaccine coverage and became low or negligible when coverage was >or=80%. Regression analysis also suggested that measles would not be transmitted when vaccine coverage was at least 79%. A minimum vaccine coverage of approximately 80% at the second birthday in census tracts, ZIP code areas, and cities in the United States may be sufficient to prevent measles transmission among preschool-aged children if population immunity is >or=93% among persons >or=6 years of age. 相似文献