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81.
Willemijn LA Sch?fer Wienke GW Boerma Anna M Murante Herman JM Sixma Fran?ois G Schellevis Peter P Groenewegen 《Bulletin of the World Health Organization》2015,93(3):161-168
Objective
To investigate patients’ perceptions of improvement potential in primary care in 34 countries.Methods
We did a cross-sectional survey of 69 201 patients who had just visited general practitioners at primary-care facilities. Patients rated five features of person-focused primary care – accessibility/availability, continuity, comprehensiveness, patient involvement and doctor–patient communication. One tenth of the patients ranked the importance of each feature on a scale of one to four, and nine tenths of patients scored their experiences of care received. We calculated the potential for improvement by multiplying the proportion of negative patient experiences with the mean importance score in each country. Scores were divided into low, medium and high improvement potential. Pair-wise correlations were made between improvement scores and three dimensions of the structure of primary care – governance, economic conditions and workforce development.Findings
In 26 countries, one or more features of primary care had medium or high improvement potentials. Comprehensiveness of care had medium to high improvement potential in 23 of 34 countries. In all countries, doctor–patient communication had low improvement potential. An overall stronger structure of primary care was correlated with a lower potential for improvement of continuity and comprehensiveness of care. In countries with stronger primary care governance patients perceived less potential to improve the continuity of care. Countries with better economic conditions for primary care had less potential for improvement of all features of person-focused care.Conclusion
In countries with a stronger primary care structure, patients perceived that primary care had less potential for improvement. 相似文献82.
We previously reported that primary neuronal cells treated with apolipoprotein E (apoE) or an apoE-derived peptide (EP) increased ERK activation and decreased JNK activation via apoE receptors. Here, we examined if the effects observed in vitro were observed in vivo. Similar to our observations in primary neurons, in vivo we found that injections of 2muM EP into the rat hippocampus increased the levels of ERK activation and decreased JNK activation. However, the time course of these effects was slower in vivo. Immunohistochemical analysis of the tissue showed prominently increased ERK phosphorylation and decreased JNK phosphorylation in neuronal cells throughout the hippocampus, particularly in the CA3 regions. To determine if apoE was endocytosed by neurons, we conjugated fluorescent microspheres with the EP and injected them into the rat hippocampus. After 7 days, the microspheres were present in neurons. We also examined the in vivo effects of apoE on ApoEr2 and APP processing. EP and full-length apoE3 and apoE4 increased C-terminal fragments of ApoEr2 and APP after a single injection, multiple injections, and chronic infusion paradigms. ApoE3 produced higher levels of ApoEr2 and APP C-terminal fragments than apoE4. These results demonstrate that apoE alters ApoEr2 and APP processing in vivo. The increase in ERK activation is consistent with a role for apoE in a neuronal response to stress, and the decrease in JNK activation suggests that apoE may have anti-apoptotic effects, over several days. 相似文献
83.
Teun P Saltzherr PH Ping Fung Kon Jin Fred C Bakker Kees J Ponsen Jan SK Luitse Mark Scholing Georgios F Giannakopoulos Ludo FM Beenen C Pieter Henny Ger M Koole Hans B Reitsma Marcel GW Dijkgraaf Patrick MM Bossuyt J Carel Goslings 《BMC emergency medicine》2008,8(1):1-5
Background
Trauma is a major source of morbidity and mortality, especially in people below the age of 50 years. For the evaluation of trauma patients CT scanning has gained wide acceptance in and provides detailed information on location and severity of injuries. However, CT scanning is frequently time consuming due to logistical (location of CT scanner elsewhere in the hospital) and technical issues. An innovative and unique infrastructural change has been made in the AMC in which the CT scanner is transported to the patient instead of the patient to the CT scanner. As a consequence, early shockroom CT scanning provides an all-inclusive multifocal diagnostic modality that can detect (potentially life-threatening) injuries in an earlier stage, so that therapy can be directed based on these findings.Methods/design
The REACT-trial is a prospective, randomized trial, comparing two Dutch level-1 trauma centers, respectively the VUmc and AMC, with the only difference being the location of the CT scanner (respectively in the Radiology Department and in the shockroom). All trauma patients that are transported to the AMC or VUmc shockroom according to the current prehospital triage system are included. Patients younger than 16 years of age and patients who die during transport are excluded. Randomization will be performed prehospitally. Study parameters are the number of days outside the hospital during the first year following the trauma (primary outcome), general health at 6 and 12 months post trauma, mortality and morbidity, and various time intervals during initial evaluation. In addition a cost-effectiveness analysis of this shockroom concept will be performed. Regarding primary outcome it is estimated that the common standard deviation of days spent outside of the hospital during the first year following trauma is a total of 12 days. To detect an overall difference of 2 days within the first year between the two strategies, 562 patients per group are needed. (alpha 0.95 and beta 0.80).Discussion
The REACT-trial will provide evidence on the effects of a strategy involving early shockroom CT scanning compared with a standard diagnostic imaging strategy in trauma patients on both patient outcome and operations research.Trial registration
ISRCTN55332315 相似文献84.
Bronchopulmonary dysplasia and very low birthweight: Lung function at 11 years of age 总被引:2,自引:0,他引:2
LW DOYLE GW FORD A. OLINSKY AML KNOCHES C. CALLANAN 《Journal of paediatrics and child health》1996,32(4):339-343
Objective : To determine the relationship between lung function at 11 years of age and bronchopulmonary dysplasia (BPD) in very low birthweight (VLBW) children.
Methodology : This study comprised 154 consecutive surviving VLBW children, divided into three groups with respect to their neonatal respiratory morbidity: group I developed BPD; group II required assisted ventilation but did not develop BPD; and group III required no assisted ventilation. Lung function tests were measured on 120/154 (77.9%) children at 11 years of age. The relationship between various lung function variables and neonatal lung disease was analysed by multiple linear regression.
Results : Several lung function variables reflecting airflow were significantly diminished in the BPD group ( n = 15), and residual volume was significantly higher. Despite poorer lung function overall, few children in the BPD group had lung function abnormalities in the clinically significant range ( n = 2 [13.3%] with a forced expired volume in 1 s <75% predicted; n = 2 [13.3%] with a forced vital capacity <75% predicted; n = 1 [6.7%] with a residual volume/total lung capacity >35%). There were no significant differences in lung function variables between group II ( n = 41) and group III ( n = 64). Changes in lung function tests between 8 and 11 years did not vary significantly between the three groups.
Conclusions : VLBW children with BPD in the newborn period have poorer lung function at 11 years of age than other surviving VLBW children without BPD, although few have lung function abnormalities in the clinically significant range. 相似文献
Methodology : This study comprised 154 consecutive surviving VLBW children, divided into three groups with respect to their neonatal respiratory morbidity: group I developed BPD; group II required assisted ventilation but did not develop BPD; and group III required no assisted ventilation. Lung function tests were measured on 120/154 (77.9%) children at 11 years of age. The relationship between various lung function variables and neonatal lung disease was analysed by multiple linear regression.
Results : Several lung function variables reflecting airflow were significantly diminished in the BPD group ( n = 15), and residual volume was significantly higher. Despite poorer lung function overall, few children in the BPD group had lung function abnormalities in the clinically significant range ( n = 2 [13.3%] with a forced expired volume in 1 s <75% predicted; n = 2 [13.3%] with a forced vital capacity <75% predicted; n = 1 [6.7%] with a residual volume/total lung capacity >35%). There were no significant differences in lung function variables between group II ( n = 41) and group III ( n = 64). Changes in lung function tests between 8 and 11 years did not vary significantly between the three groups.
Conclusions : VLBW children with BPD in the newborn period have poorer lung function at 11 years of age than other surviving VLBW children without BPD, although few have lung function abnormalities in the clinically significant range. 相似文献
85.
LRP and senile plaques in Alzheimer's disease: colocalization with apolipoprotein E and with activated astrocytes 总被引:7,自引:0,他引:7
Arélin K Kinoshita A Whelan CM Irizarry MC Rebeck GW Strickland DK Hyman BT 《Brain research. Molecular brain research》2002,104(1):38-46
The low density lipoprotein receptor-related protein (LRP) is a multifunctional receptor which is present on senile plaques in Alzheimer's disease (AD). It is suggested to play an important role in the balance between amyloid beta (Abeta) synthesis and clearance mechanisms. One of its ligands, apolipoprotein E (apoE), is also present on senile plaques and has been implicated as a risk factor for AD, potentially affecting the deposition, fibrillogenesis and clearance of Abeta. Using immunohistochemistry we show that LRP was present only on cored, apoE-containing senile plaques, in both PDAPP transgenic mice and human AD brains. We detected strong LRP staining in neurons and in reactive astrocytes, and immunostaining of membrane-bound LRP showed colocalization with fine astrocytic processes surrounding senile plaques. LRP was not present in plaques in young transgenic mice or in plaques of APOE-knockout mice. As LRP ligands associated with Abeta deposits in AD brain may play an important role in inducing levels of LRP in both neurons and astrocytes, our findings support the idea that apoE might be involved in upregulation of LRP (present in fine astrocytic processes) and act as a local scaffolding protein for LRP and Abeta. The upregulation of LRP would allow increased clearance of LRP ligands as well as clearance of Abeta/ApoE complexes. 相似文献
86.
Dose-dependent localization of TCDD in isolated centrilobular and periportal hepatocytes 总被引:3,自引:1,他引:2
Santostefano MJ; Richardson VM; Walker NJ; Blanton J; Lindros KO; Lucier GW; Alcasey SK; Birnbaum LS 《Toxicological sciences》1999,52(1):9-19
Dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
suggest a differential sensitivity of liver cell types to the induction of
cytochrome P450 gene expression, and that the induction of hepatic protein
CYP1A2 causes sequestration of TCDD. In addition, immunolocalization of
hepatic CYP1A1/1B1/1A2 proteins is not uniform after exposure to TCDD. The
mechanism for the regio-specific induction of hepatic P450s by TCDD is
unknown, but may involve the differential distribution of participants in
the AhR-mediated pathway and/or regional P450 isozymes, as well as,
non-uniform distribution/sequestration of TCDD. Therefore, this study
examined the effects of TCDD in unfractionated, centrilobular and
periportal hepatocytes isolated from female Sprague-Dawley rats acutely
exposed (3 days) to a single oral dose of 0.01-10.0 microg [3H]TCDD/kg. A
dose- dependent increase in concentration of TCDD was accompanied by a
dose- dependent increase in CYP1A1, CYP1A2, and CYP1B1 mRNA expression and
associated enzymes in all liver-cell populations. Centrilobular hepatocytes
showed a 2.7- to 4.5-fold higher concentration of TCDD as compared to the
periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Centrilobular
hepatocytes also exhibited an elevated MROD activity as compared to the
periportal hepatocytes at doses up to 0.3 microg TCDD/kg. Furthermore,
centrilobular hepatocytes showed an elevated concentration of induced
CYP1A2 and CYP1B1 mRNA as compared to periportal hepatocytes within the
0.01- and 0.3-microg TCDD/kg- treatment groups. This is the first study to
demonstrate that a dose- dependent difference in distribution of TCDD
exists between centrilobular and periportal cells that might be related to
regional differences in P450 induction.
相似文献
87.
Mooney LA; Bell DA; Santella RM; Van Bennekum AM; Ottman R; Paik M; Blaner WS; Lucier GW; Covey L; Young TL; Cooper TB; Glassman AH; Perera FP 《Carcinogenesis》1997,18(3):503-509
Prior epidemiological evidence suggests that genes controlling the
metabolism of carcinogens and antioxidant/nutritional status are associated
with lung cancer risk, possibly through their ability to modulate DNA
damage by carcinogens. We performed a cross-sectional analysis of 159 heavy
smokers from a cohort of subjects enrolled in a smoking cessation program.
A total of 159 blood samples were analyzed to determine the relative
contributions of genetic polymorphisms [CYP1A1 MspI and exon 7 and
glutathione S-transferase M1 (GSTM1)] and plasma micronutrients to
polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adduct levels. DNA damage in
smokers was affected by genetic polymorphisms and nutritional status.
Smokers with the CYP1A1 exon 7 valine polymorphism had significantly higher
(2-fold, P < or = 0.03) levels of DNA damage than those without. In
parallel models, PAH-DNA adducts were inversely associated with plasma
levels of retinol (beta = -0.93, P = 0.01), beta-carotene (beta = -0.18, P
= 0.09), and alpha- tocopherol (beta = -0.28, P = 0.21) in 159 subjects.
The association between smoking-adjusted plasma beta-carotene levels and
DNA damage was only significant in those subjects lacking the GSTM1
detoxification gene (beta = -0.30, P = 0.05, n = 75). There was a
statistical interaction between beta-carotene and alpha-tocopherol; when
beta- carotene was low, alpha-tocopherol had a significant protective
effect (beta = -0.78, P = 0.04) on adducts, but not when beta-carotene was
high (beta = -0.16, P = 0.57). Plasma alpha-tocopherol was significantly
correlated with beta-carotene (r = 0.36, P = 0.0005) and less strongly with
retinol (r = 0.20, P = 0.0005). These results suggest that several
micronutrients may act in concert to protect against DNA damage and
highlight the importance of assessing overall antioxidant status. In
conclusion, a subset of smokers may be at increased risk of DNA damage and
possibly lung cancer due to the combined effect of low plasma
micronutrients and genetic susceptibility factors. The use of biological
markers to assess efficacy of interventions and to study mechanisms of
micronutrients is timely given the current debate regarding the use of
chemopreventive agents in high risk populations.
相似文献
88.
89.
Lack of association of the cholesterol 24-hydroxylase (CYP46) intron 2 polymorphism with Alzheimer's disease 总被引:5,自引:0,他引:5
An association was recently reported between an increased risk of Alzheimer's disease and an intron 2 AA genotype of CYP46, the enzyme hydroxylating cholesterol to 24S-hydroxycholesterol. Moreover, CYP46 AA-carriers were found to have increased levels of amyloid-beta and tau in brain and cerebrospinal fluid. We determined the CYP46 intron 2 genotype in a cohort of 178 AD and 105 non-demented control subjects, but found no significant association with AD for any of the individual genotypes or alleles. Further, in an autopsy confirmed subset of this cohort, the proposed CYP46 risk genotype was not associated with any increase in the brain levels of amyloid-beta40, amyloid-beta42 or in the levels of amyloid plaques and neurofibrillary tangles. Despite growing evidence implicating cholesterol metabolism in AD risk and Abeta generation, our data does not support a robust genetic relationship between the CYP46 intron 2 polymorphism and AD risk or neuropathology. 相似文献
90.
Apolipoprotein E (apoE) alters the pathophysiology of Alzheimer's disease, but its mechanism is not fully understood. We examined the effects of recombinant human apoE3 and apoE4 on the neuronal calcium response to N-methyl-D-aspartate (NMDA), and compared them to their toxicity. ApoE4 (100 nM) significantly increased the resting calcium (by 70%) and the calcium response to NMDA (by 185%), whereas similar changes were not obtained in apoE3-treated neurons. ApoE4, but not apoE3, also significantly increased neurotoxicity, as evidenced by enhanced lactate dehydrogenase release (by 53%) and reduced 3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide levels (by 32%). ApoE4-induced changes in the calcium response to NMDA and associated neurotoxicity were blocked by coincubation with MK-801. Both the receptor-associated protein, which inhibits interaction of apoE with members of the LDL receptor family, including the low-density lipoprotein receptor-related protein (LRP), and activated alpha2-macroglobulin, another LRP ligand, prevented apoE4-induced enhancement of the calcium response to NMDA, resting calcium levels, and neurotoxicity. A tandem apoE peptide (100 nM) containing only the receptor binding region residues also eliminated the enhanced calcium signaling and neurotoxicity by apoE4. Taken together, our data demonstrate that differential effects of apoE3 and apoE4 on the calcium signaling in neurons correlate with their effect on neurotoxicity, which are secondary to receptor binding. 相似文献