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991.
Amanda J Leach Peter S Morris Gabrielle B McCallum Cate A Wilson Liz Stubbs Jemima Beissbarth Susan Jacups Kim Hare Heidi C Smith-Vaughan 《BMC infectious diseases》2009,9(1):121-9
Background
In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule. 相似文献992.
993.
Matthew Wheeler Aleksandra Pavlovic Emil DeGoma Heidi Salisbury Colleen Brown Euan A. Ashley 《Journal of cardiovascular translational research》2009,2(4):381-391
Building on seminal studies of the last 20 years, genetic testing for hypertrophic cardiomyopathy (HCM) has become a clinical
reality in the form of targeted exonic sequencing of known disease-causing genes. This has been driven primarily by the decreasing
cost of sequencing, but the high profile of genome-wide association studies, the launch of direct-to-consumer genetic testing,
and new legislative protection have also played important roles. In the clinical management of hypertrophic cardiomyopathy,
genetic testing is primarily used for family screening. An increasing role is recognized, however, in diagnostic settings:
in the differential diagnosis of HCM; in the differentiation of HCM from hypertensive or athlete’s heart; and more rarely
in preimplantation genetic diagnosis. Aside from diagnostic clarification and family screening, use of the genetic test for
guiding therapy remains controversial, with data currently too limited to derive a reliable mutation risk prediction from
within the phenotypic noise of different modifying genomes. Meanwhile, the power of genetic testing derives from the confidence
with which a mutation can be called present or absent in a given individual. This confidence contrasts with our more limited
ability to judge the significance of mutations for which co-segregation has not been demonstrated. These variants of “unknown”
significance represent the greatest challenge to the wider adoption of genetic testing in HCM. Looking forward, next-generation
sequencing technologies promise to revolutionize the current approach as whole genome sequencing will soon be available for
the cost of today’s targeted panel. In summary, our future will be characterized not by lack of genetic information but by
our ability to effectively parse it. 相似文献
994.
995.
Ingmar Meinecke Gza Pap Heidi Mendoza Steffen Drange Stephan Ender Simon Strietholt Renate E. Gay Christine Seyfert Barbara Ink Steffen Gay Thomas Pap Marvin A. Peters 《Arthritis \u0026amp; Rheumatology》2009,60(7):2065-2070
Objective
To study the expression of small ubiquitin‐like modifier 1 (SUMO‐1) in aseptic loosening of prosthesis implants and to investigate its role in regulating the susceptibility of prosthesis‐loosening fibroblast‐like synoviocytes (FLS) to Fas‐induced apoptosis.Methods
Specimens of aseptically loosened tissue were obtained at revision surgery, and the expression of SUMO‐1 was analyzed by in situ hybridization. SUMO‐1 levels in FLS were determined by quantitative polymerase chain reaction and Western blot analysis. Immunohistochemistry and confocal microscopy were used to study the subcellular localization of SUMO‐1. The functional role of SUMO‐1 in Fas‐induced apoptosis of prosthesis‐loosening FLS was investigated by small interfering RNA–mediated knockdown of SUMO‐1 and by gene transfer of the nuclear SUMO‐specific protease SENP1.Results
SUMO‐1 was expressed strongly in aseptically loosened tissue and was found prominently at sites adjacent to bone. Prosthesis‐loosening FLS expressed levels of SUMO‐1 similar to the levels expressed by rheumatoid arthritis (RA) FLS, with SUMO‐1 being found mainly in promyelocytic leukemia protein nuclear bodies. Knockdown of SUMO‐1 had no effect on spontaneous apoptosis but significantly increased the susceptibility of prosthesis‐loosening FLS to Fas‐induced apoptosis. Gene transfer of the nuclear SUMO‐specific protease SENP1 reverted the apoptosis‐inhibiting effects of SUMO‐1.Conclusion
These data suggest that SUMO‐1 is involved in the activation of both RA FLS and prosthesis‐loosening FLS by preventing these cells from undergoing apoptosis. Modification of nuclear proteins by SUMO‐1 contributes to the antiapoptotic effects of SUMO‐1 in prosthesis‐loosening FLS, providing evidence for the specific activation of sumoylation during their differentiation. Therefore, SUMO‐1 may be an interesting target for novel strategies to prevent aseptic prosthesis loosening.996.
Heidi K. White MD Gwendolen T. Buhr MD Sandro O. Pinheiro PhD 《Journal of the American Geriatrics Society》2009,57(7):1270-1277
Mentoring is an important instructional strategy that should be maximally used to develop the next generation of physicians who will care for a growing population of frail older adults. Mentoring can fulfill three specific purposes: (1) help learners choose an area of specialty, (2) help fellows and new faculty navigate advancement in the academic environment, and (3) help new physicians enter a local medical community and develop a high-quality, professionally rewarding, financially viable practice that meets the needs of older adults. The components and process of mentoring are reviewed. Current and potential mechanisms to promote mentoring for the specific purpose of increasing the quality and quantity of physicians available to care for the older adult population are discussed. 相似文献
997.
998.
Anne-Mette Bay Bjørn Peter Jepsen Heidi Jeanet Larsson Henrik Frederik Thomsen Helle Kieler Vera Ehrenstein & Steffen Christensen 《Addiction (Abingdon, England)》2009,104(1):104-108
Aims To assess hospitalization rates (HR) for poisoning with heroin, methadone or strong analgesics and relate them to quantities of prescribed methadone and strong analgesics in Denmark between 1998 and 2004.
Design Population-based ecological study.
Settings We extracted data on all emergency department visits and hospital admissions registered in the Danish National Patient Registry with a diagnosis of poisoning with heroin ( n = 1688), methadone ( n = 173) or strong analgesics ( n = 384). To ascertain sale of prescribed medications we used data from the Danish Medicines Agency.
Measurements Age- and gender-standardized HR and defined daily doses (DDD) per 1000 people per day.
Findings HR for heroin poisoning was 4.4 [95% confidence interval (CI): 3.8–4.9] per 100 000 person-years (p-y) in 1998 and 4.6 (CI: 4.0–5.2) per 100 000 p-y in 2004. HR for methadone poisoning increased from 0.1 (CI: 0.0–0.2) per 100 000 p-y in 1998 to 1.1 (CI: 0.8–1.4) per 100 000 p-y in 2004. HR for poisoning with strong analgesics increased from 0.6 (CI: 0.4–0.9) per 100 000 p-y in 1998 to 2.1 (CI: 1.8–2.6) per 100 000 p-y in 2004. The sale of prescribed strong analgesics (5.0 DDD per 1000 people per day in 1998 to 5.9 DDD in 2004) and methadone (3.0 DDD per 1000 people per day in 1998 to 3.4 DDD in 2004) increased slightly between 1998 and 2004.
Conclusion Increasing sale of prescribed methadone and strong analgesics coincided with increasing HRs of poisoning with these drugs, whereas HR of heroin poisoning varied. Further longitudinal studies are important for the guidance of future policy making. 相似文献
Design Population-based ecological study.
Settings We extracted data on all emergency department visits and hospital admissions registered in the Danish National Patient Registry with a diagnosis of poisoning with heroin ( n = 1688), methadone ( n = 173) or strong analgesics ( n = 384). To ascertain sale of prescribed medications we used data from the Danish Medicines Agency.
Measurements Age- and gender-standardized HR and defined daily doses (DDD) per 1000 people per day.
Findings HR for heroin poisoning was 4.4 [95% confidence interval (CI): 3.8–4.9] per 100 000 person-years (p-y) in 1998 and 4.6 (CI: 4.0–5.2) per 100 000 p-y in 2004. HR for methadone poisoning increased from 0.1 (CI: 0.0–0.2) per 100 000 p-y in 1998 to 1.1 (CI: 0.8–1.4) per 100 000 p-y in 2004. HR for poisoning with strong analgesics increased from 0.6 (CI: 0.4–0.9) per 100 000 p-y in 1998 to 2.1 (CI: 1.8–2.6) per 100 000 p-y in 2004. The sale of prescribed strong analgesics (5.0 DDD per 1000 people per day in 1998 to 5.9 DDD in 2004) and methadone (3.0 DDD per 1000 people per day in 1998 to 3.4 DDD in 2004) increased slightly between 1998 and 2004.
Conclusion Increasing sale of prescribed methadone and strong analgesics coincided with increasing HRs of poisoning with these drugs, whereas HR of heroin poisoning varied. Further longitudinal studies are important for the guidance of future policy making. 相似文献
999.
Zhen Xu Heidi M. Mansour Tako Mulder Richard McLean John Langridge Anthony J. Hickey 《Journal of pharmaceutical sciences》2010,99(8):3415-3429
The objectives of this study were: systematic investigation of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs; mechanistic evaluation of performance data by powder aerosol deaggregation equation (PADE). The drugs (IPB and FP) were prepared in sieved and milled lactose carriers (2% w/w). Aerosol studies were performed using SETs (shear stresses τs = 0.624-13.143 N/m2) by twin-stage liquid impinger, operated at 60 L/min. PADE was applied for formulation screening. Excellent correlation was observed when PADE was adopted correlating FPF to τs. Higher τs corresponded to higher FPF values followed by a plateau representing invariance of FPF with increasing τs. The R2 values for PADE linear regression were 0.9905-0.9999. Performance described in terms of the maximum FPF (FPFmax: 15.0–37.6%) resulted in a rank order of ML-B/IPB > ML-A/IPB > SV-A/IPB > SV-B/IPB > ML-B/FP > ML-A/FP > SV-B/FP > SV-A/FP. The performance of IPB was superior to FP in all formulations. The difference in lactose monohydrate carriers was less pronounced for the FPF in IPB than in FP formulations. The novel PADE offers a robust method for evaluating aerodynamic performance of dry powder formulations within a defined τs range. 相似文献
1000.
Koivisto H Hietala J Anttila P Parkkila S Niemelä O 《The Journal of laboratory and clinical medicine》2006,147(4):191-196
Although excessive alcohol consumption is known to elevate the mean cell volume (MCV) of erythrocytes, the relationships among the intensity of ethanol exposure, the generation of abnormal red blood cell indices, and the underlying pathogenic mechanisms have remained unclear. The authors examined 105 alcoholics with a wide range of ethanol consumption (40-500 g of ethanol/day), 62 moderate drinkers (mean consumption 1-40 g/day), and 24 abstainers, who underwent detailed interviews, measurements of blood cell counts, markers of liver status, and circulating antibodies against ethanol-derived protein modifications. Follow-up information was collected from healthy volunteers with detailed records on drinking habits. Data from the NORIP project for laboratory parameters in apparently healthy moderate drinkers or abstainers (n = 845) were used for reference interval comparisons. The highest MCV (P < 0.001) and mean cell hemoglobin (MCH) (P < 0.01) occurred in the alcoholics. However, the values in the moderate drinkers also responded to ethanol intake such that the upper normal limit for MCV based on the data from moderate drinkers was 98 fl, as compared with 96 fl from abstainers. Follow-up cases with carefully registered drinking habits showed parallel changes in MCV and ethanol intake. Anti-adduct IgA and IgM against acetaldehyde-induced protein modifications were elevated in 94% and 64% of patients with high MCV, respectively, the former being significantly less frequent in the alcoholics with normal MCV (63%) (P < 0.05). The data indicate dose-related responses in red blood indices upon chronic ethanol consumption, which may also be reflected in reference intervals for hematological parameters in health care. Generation of immune responses against acetaldehyde-modified erythrocyte proteins may be associated with the appearance of such abnormalities. 相似文献